Anticancer Plants Naturally Growing in Al-Baha Region, Saudi Arabia

 

Khulud Mohammed Alshehri

Department of Biology, Al-Baha University, Baljurashi, Saudi Arabia.


ABSTRACT

Medicinal plants have traditionally been used worldwide, including in Saudi Arabia. Globally, medicinal plants have received much attention because of their promising potential for use as anticancer treatments for different types of cancer, and their phytochemicals play a major role in biological reactions, such as in mediating cytotoxicity against cancer cell lines. This review highlights some important genera that belong to different naturally occurring plant families in the Al-Baha region and describes their importance in cancer treatment. To date, the anticancer effects of some medicinal plants that grow naturally in the Al-Baha region have been used in cancer treatment. Various electronic databases from 1990 to 2020 were searched for articles that reported the efficacy of 19 local plants against a wide range of cancer cell lines. Data collected included the plant part used, method of extraction, type of cancer cell line, and the effectiveness of the extract as an anticancer agent. Each of the 11 plant families (Amaranthaceae, Leguminosae, Apocynaceae, Vitaceae, Burseraceae, Capparaceae, Compositae, Curcurbitaceae, Oleaceae, Papaveraceae, and Rhamnaceae) included in this review had at least one genus that was considered a source of anticancer agents. Twenty-one plants from the Al-Baha region were assessed for their anticancer activities worldwide. The extracts of all tested plants showed significant results on different cell lines, and these important plant families have various conventional and novel uses in daily life.

Key words: Al-Baha region, anticancer plants, plant extracts, cancer cell line, cytotoxicity


INTRODUCTION

In humans, cancer is the most conspicuous disease that leads to death [1, 2]. The abnormal growth and proliferation of cancer cells lead to life-threatening complications, which pose an immense health burden and cause approximately 6 million deaths every year, worldwide [3, 4]. The high cancer mortality rate is associated with the serious adverse effects of anticancer therapies, such as chemotherapy and radiation therapy, that may motivate many cancer patients to switch to alternative medicine [5, 6]. Lung, prostate, colorectal, stomach, breast, and cervical cancers are the most common and prevalent types of cancers. Thus, traditional medicine has become a topic of global health importance, given its widespread use in the treatment of several diseases worldwide [7, 8].

Several plant genera are utilized by various systems of medicine to treat various diseases [9]. In recent years, however, attention has been focused increasingly on identifying natural substances that are capable of inhibiting multistage carcinogenesis [10]. Medicinal plants are a major source of traditional medicines, modern medicines, nutraceuticals, and pharmaceutical intermediates [11]. Furthermore, medicinal plants are considered to be a chemical resource for the pharmaceutical industry, which have recently gained much interest owing to their wide range of applications [12].

The synergistic properties and polypharmacological applications of plant extracts are most notable with regard to several significant outcomes that have been achieved through the use of natural products in the treatment of diseases [13]. Therefore, considerable scientific research is directed toward the identification of novel natural-occurring substances that could potentially cure patients with different diseases [14]. The Al-Baha province is located in the southwest region of Saudi Arabia and comprises a plethora of geographical regions that create a huge depository for medicinal plants, which have increasingly gained popularity in traditional medical treatments [15]. The high mountain ranges of the Al Baha province are considered to be some of the most significant plant diversity zones in Saudi Arabia, estimated to contain approximately 230 species (~12% of the total plant species of ) [16]. This review was undertaken with an objective to analyze the available data on the research that has been performed to date on the natural growth of some medicinal plants in the Al-Baha region.

 

METHODOLOGY

Scientific studies were identified through searches of various electronic databases (Medline, PubMed, Science Direct, Scopus, and Google Scholar websites) for articles published from 1990 to 2020. A comprehensive search of naturally growing anticancer plants in the Al-Baha region of Saudi Arabia turned up a total of 83 publications that were included in this review. In this review, the families and scientific names of plant species were checked for the latest changes according to “The Plant List” (http://www.theplantlist.org). Using a qualitative approach, data were collected from the included studies for the identification of characteristics, such as the plant part used, method of extraction, type of cancer cell lines, and the effectiveness of the extract as an anticancer agent (Table 1).

 

DISCUSSION

The electronic database searches led to the identification of 83 relevant studies that tested the anticancer efficacy of some species of medicinal plants. Based on an inventory and documentation of flora in the articles from the Al-Baha Province, Saudi Arabia, plant species were selected for inclusion in this study [17-21]. The eligible studies focused on the different methods of phytochemical extraction from different parts of the plants and described the in vitro investigation of the anticancer effect of these plants against various cancer cell lines. The Amaranthaceae family is a commonly growing plant family that grows in tropical to cool-temperate regions and comprises approximately 180 genera and 2500 species. Chemical characterization indicates the presence of several bioactive compounds in these plants, and these phytochemicals include phenolic acid, flavonoids, tannins, saponins, and triterpenoids [22, 23]. Chenopodium album L. (C. album) belongs to the family Amaranthaceae, and its leaves have a relatively high content of total phenolics and carnosol, which are activated as antioxidants and show promising potential for preventing certain types of cancer, especially skin melanomas [24].

Various solvent extracts (Pt. ether, EtOAc, and MeOH) of C. album leaves have been screened for cytotoxic activity against the MCF-7 human breast cancer cell lines and MDA-MB-468 that was tested in an MTT bioassay [25]. Moreover, phytochemical extracts from C. album leaves showed inhibitory effects on the growth of lung cancer A549 cells. The PE extract inhibited cell growth in the A549 cell line in a time- and dose-dependent manner, as determined via MTT and colony-formation assays [26]. The MCF7 cells were sensitive to treatment with the ethyl acetate and methanol extracts of C. album, which prevented cancer cell growth [25].

Chenopodium ambrosioides L., Amaranthus spinosus, Achyranthes aspera, Aerva javanica, and Aerva lanata belong to the Amaranthaceae family. C. ambrosioides is one of the 24 species that have been observed at different sites along the catchment area of the Al-Baha region [19]. Essential oils from C. ambrosioides were shown to affect human breast cancer MCF-7 cells, as assessed by the MTT assay. The proliferation of MCF-7 cells was inhibited after treatment with C. ambrosioides essential oil that was extracted from the branches and leaves. The cytotoxicity of the essential oil extract affected on MCF-7 cells in a concentration- and time-dependent manner [27].

A. spinosus leaf extracts were shown to have an effect on cell proliferation, leading to the inhibition of cancer cell growth, in the LNCaP prostate cancer cell lines by using MTT assays [28]. A. aspera root extracts have been tested for anticancer activity, and the aqueous extract of A. aspera suppressed cell proliferation and increased cytotoxicity in COLO-205 colon cancer cells in a time- and dose-dependent manner when tested using a clonogenic cell survival assay. The estimated antiproliferative effect of the A. aspera aqueous extract showed an ability to decrease the cell division and colony-forming capacity of cancer cells. Therefore, the aqueous and ethanolic extracts of A. aspera contain phytochemical complexes that may serve as an abundant source of bioactive compounds for the management of colon cancer.

The antioxidant assay proved that the ethanolic extracts of A. aspera have a greater ability to scavenge free radicals. A cell viability assay was conducted to determine the effect of the aqueous extract of A. aspera roots on the viability of COLO-205 cells, and the results showed a time- and dose-dependent response in growth inhibition, which was more noticeable in the aqueous extract of A. aspera [29].

The methanolic extracts of A. javanica leaves inhibited the growth of MCF-7 cell line with a minimal reduction of viability and proliferation abilities, as observed in the in vitro experiments using the MTT assay [30]. The anticancer effect of A. lanata extracts obtained from the fresh aerial parts of the plant on Dalton’s Ascitic Lymphoma (DAL) cell line in Swiss albino mice was most likely due to its cytotoxic potential and reduced the cancer cell count, which affirms its indication as a protective agent against DAL. The presence of terpenoids, alkaloids, and flavonoids may contribute to the anticancer characteristics of the extracts [31].

The Leguminosae family is one of the largest botanical families and comprises approximately 770 genera and 19,500 species [32]. A large range of natural products, including flavors, poison, and dyes, are synthesized from Leguminosae plants and they have great importance in medicinal purposes [33] Acacia ehrenbergiana, Acacia tortilis, Astragalus vogelii, and Tamarindus indica constitute the Al-Baha flora that belong to the Leguminosae family.

The ethanolic extract of A. ehrenbergiana yellow flowers has been shown to have potential anticarcinogenic activity against three cancer cell lines: A2780 (human ovarian adenocarcinoma), MCF7 (human breast adenocarcinoma), and HT29 (human colon adenocarcinoma). The anti-proliferative effect of the ethanol extract of A. ehrenbergiana Hayne was attributed to saponins, alkaloids, flavonoids, tannins, and other phytoconstituents that have been identified in the flowers of these plants in the southern part of Saudi Arabia [34].

The ethanolic extracts of the fresh leaves of the Saudi Arabian plant A. tortilis (Forssk.) showed significant cytotoxic activity against kidney carcinoma (HEK-293), human liver cancer (HepG2), and human breast cancer (MCF-7) cell lines [35]. The cytotoxic activity of A. tortilis extracts has been attributed to phenolic compounds that influence the specific mechanisms, including the cell cycle, cell death, and apoptosis, that are involved in tumor proliferation [36].

The methanol extracts of the aerial parts of A. vogelii have been shown to have time- and dose-dependent cytotoxic activity against the human Caco-2 (colon cancer) and A549 (lung cancer) cell lines, as assessed using the MTT assay. This cytotoxic potential of A. vogelii extracts is explained by the richness of phenolic, flavonoids, and tannin compounds in A. vogelii that have a natural antioxidant activity and may contribute to their medicinal characteristics [37]. The in vitro antiproliferative activity of a polysaccharide, PST001, that was isolated and purified from the seed kernel of T. indica has been documented against the cancer cell lines MCF-7, A549, DLA, KB, and EAC. Furthermore, this polysaccharide induced in vitro immunomodulatory activities, including phagocytic enhancement and inhibition of leukocyte migration in normal cells, besides the antiproliferative activity on cancer cells [38].

Apocynaceae is a large family of flowering plants that includes vines, herbs, shrubs, stem, and succulents [39]. A significant number of characteristic chemical structures, mainly alkaloids, that are typical derivatives of plants belonging to the Apocynaceae family have been considered to be potential antileishmanial agents [40, 41]. Carissa carandas L., Carissa spinarum L., and Calotropis procera are medicinal plants from the Apocynaceae family that are found in the Al Baha region. C. carandas L. is considered a medicinal source because of the presence of photochemically active substances, including saponins, cardiac glycosides, phenolic components, flavonoids, triterpenoids, and alkaloids. The extract of C. carandas leaves that is obtained using n-hexane, methanol, and chloroform as the solvents has a significant anticancer effect against lung cancer and ovarian carcinoma cell lines [42]. In another study, the anticancer and antioxidant activities of C. carandas leaf aqueous extracts were examined in the MCF-7 cancer cell line, and the leaf extracts showed significant antioxidant activity and led to the prevention of cell death [43]. The extracts of the stem of C. spinarum L. contain potential anticancer agents that may have therapeutic effects against colon (Colo-205 and SW-620), ovarian (IGR-OV-1 and OVCAR-5), prostate (DU-145 and PC-3), lung (Hop-62 and A-549), CNS (SK-N-SH and SF-295), acute promyelocytic leukemia (HL-60), and acute lymphoblastic leukemia (MOLT-4) cell lines.

C. spinarum produces various sesquiterpenes, cardiac glycosides, and flavonoids, such as naringenin, as well as triterpene acids, such as ursolic acid, which confer the anticancer effect of the C. spinarum extracts [44]. The root extract of C. procera has been shown to have an intense cytotoxic effect on COLO-320 tumor cells [45].

The Vitaceae family consists of 14 genera and about 900 species that are spread across the tropical regions of Africa, Asia, the Neotropics, Australia, and the Pacific islands [46]. The Cissus quadrangularis is an Al Baha plant that belongs to the Vitaceae family. The ethanolic extract of C. quadrangularis shows potent anticancer activity against the Ehrlich adenocarcinoma, A431 (skin epithelial carcinoma), KB (oral epidermoid carcinoma), HeLa (cervical cancer), MCF7 (breast cancer), HT29 (colon carcinoma), Vero (kidney epithelial cell), and HEp 2 (human laryngeal carcinoma) cell lines [47, 48].

Jun et al., 2017 [49] confirmed the anticancer activity of curcumin against MG-63 osteosarcoma cells and subsequently characterized the phytochemical constituents of curcumin. The curcumin stem contains phosphorous and calcium, which help in bone formation. Some of the essential phytochemicals in curcumin include amyrins (a and b), carotene, vitamin C, resveratrol, β-sitosterol, flavonoids such as quadrangularis (A, B, and C), quercetin, and kaempferol [50], and provides a better understanding of the anticancer activity of curcumin against bone tumors [51]. The methanolic extract of C. quadrangularis showed cytotoxic activity against MG63 cells in a dose-dependent manner. Furthermore, the methanolic extract obtained from the aerial parts of C. quadrangularis showed antiproliferative activity against MG63 cells on a cytotoxicity assay [52].

The Burseraceae family is speculated to have originated in the Eocene period in North America. In its migration through the tropical and subtropical regions worldwide, the Burseraceae family, with 18 known genera and about 700 species, has dispersed throughout the southern American terrain and Europe, later reached Africa, Asia, and Oceania [53].

Commiphora gileadensis belongs to the Burseraceae family, is commonly known as the Balm of Mecca, and has widespread distribution near the Red Sea, especially within the border areas of the KSA, Oman, Eritrea, and Yemen [54]. C. gileadensis is an evergreen medium-sized aromatic shrub, which grows in East Africa and Arabia and is considered to be an important medicinal plant in Saudi Arabia [55]. Aliphatic alcohol glycosides, triterpenoids, sesquiterpenoids, and several new cycloartane types were isolated recently from the crushed resin of C. gileadensis, and the cytotoxic effect of C. gileadensis, especially against human prostate, liver, and cervical cancer cell lines, was attributed to these phytochemicals [56]. β-caryophyllene is an active component in the ethanolic extracts of C. gileadensis and inhibits growth and induce apoptosis in two lymphocytic tumor cell lines [57]. Skin cancer is characterized by hyperproliferative pathology, and skin cancer cells are typically resistant to programmed cell death [58]. Several therapeutic uses of C. gileadensis have been reported and include the antiproliferative properties of the ethanolic extract of C. gileadensis sap in cancer cell lines, especially in strongly inducing apoptosis in immortalized and transformed human epidermal cell lines [56, 59].

Capparaceae comprises a medium-sized family of about 45 genera and 700–900 species, and whose members exhibit considerable variation in their habitat [60]. The twigs and stem extract of Capparis cartilaginea showed the highest cytotoxic activity against the cellosaurus cell line A549. However, a previous study reported the absence of any cytotoxic effect of the leaf extract of C. cartilaginea on lung (A-427), urinary bladder (5637), and breast (MCF-7) cancer cell lines [61]. Moreover, the methanol extract of the flowering branch of C. cartilaginea exhibited no cytotoxic effect against cancer cells, including the MCF-7, human hepatocellular carcinoma (HepG-2), mouse fibrosarcoma (WEHI-164), A549, and Madin–Darby bovine kidney (MDBK) cell lines [62, 63].

The family Asteraceae ranks high in Angiosperm phylogeny in Asterideae/Asterales and includes the largest number of species (~30,000) among all plant families and has 1600-1700 plant genera that are distributed worldwide, excluding Antarctica [64].

Achillea Biebersteinii grows wild in untended agricultural fields in the Al Baha region. A. Biebersteinii extract showed a cytotoxic effect on sex-types of cancer cell lines, including human Caucasian gastric adenocarcinoma (AGS), human liver hepatoma (NCBI C136: PLC/PRF/5), human melanoma cancer cell (NCBI C566: A375), human lung carcinoma (NCBI C146: SKLC6), human colorectal adenocarcinoma (NCBI C135: SW742), human breast ductal carcinoma (NCBI C131: MCF7), primary cell culture of human fetal foreskin fibroblasts (NCBI C145: HFFF), and (NCBI C170) [65].

Cucurbitaceae is a medium-sized family that consists of approximately 120 genera and more than 800 species that are predominantly distributed in the tropical and subtropical regions of the New and Old World [66]. The leaf extract of C. colocynthis revealed growth inhibitory activity against human breast cancer cell lines in a time- and dose-dependent manner, as shown in an MTT assay in MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) cell lines [67]. The antiproliferative effects of extracts from different parts of C. colocynthis were investigated in different cancer cell lines; the chloroform-derived leaf extract conferred a high potential for the inhibition of cancer cell growth in human colon cancer cells (HT-29) when tested by using the MTS and a model alkaline comet assay protocol [68]. The anticancer effect of C. colocynthis fruit juice extracts was studied in human cancer cells and resulted in a significant reduction in the proliferation of MCF-7, HepG-2, and breast cancer cells [69, 70]. Furthermore, the rate of cell growth of breast cancer cells (MCF-7) treated with the C. colocynthis fruit extract decreased in cancer cells compared with that in the control group [71].

Oleaceae is a family of dicotyledonous flowering plants that are commonly distributed throughout temperate and tropical regions and includes 25 genera and approximately 688 species [72]. Olea europaea is an evergreen tree and its leaves are obtained during the pruning process in olive farming [73]. Bioactive compounds, such as tannins, carbohydrates, and amino acids, were abundantly found in the leaves of the Leccino and Carolea cultivars of O. europaea [73], and the O. europaea leaf extract induced toxicity in breast cancer cell lines [74].

Papaveraceae (poppy family) is one of the families of angiosperms and includes 26–42 genera and 690–800 species worldwide [75]. This family has a widespread distribution and is found especially in the Mediterranean region; central, eastern, and western Asia; India; America; middle Europe; and southern regions of Scandinavia and Great Britain [76]. The anticancer and antiproliferative activities of Argemone mexicana extracts were tested in the human cancer cell lines HeLa-B75, HL-60, HEP-3B, and PN-15, and the results indicated that A. mexicana is a medicinal plant that can be considered to be a potential resource for anticancer agents [77]. The ethanolic extract of A. mexicana exhibited inhibitory activity against human cancer cell lines, such as HeLa-B75, HL-60, and PN-15 [78]. In addition, the methanolic extract of A. mexicana leaves showed great anticancer activity against the HeLa and MCF-7 cancer cell lines. Based on the results of the MTT assay, the researchers proved that the cytotoxic activity was apoptotic rather than necrotic, which was possibly due to the presence of flavonoid constituents in the leaves [79]. A. mexicana stem and leaf extracts exhibited significant cytotoxicity in the A549 human lung carcinoma cell line [80].

Rhamnaceae is a cosmopolitan family of small trees, shrubs, and climbers that has been divided into three major groups based on recent taxonomic revisions [81]. Furthermore, Rhamnaceae includes approximately 60 genera distributed among 11 tribes, with some notable ambiguity. For example, the large genus Ceanothus L. (~50 spp.) has not yet been attributed to any tribe [82]. The total extract of Ziziphus spina christi and its ethanol, ethanolaqueous, and aqueous fractions inhibited the proliferation of MCF-7 cells. The ethanolic fraction was highly active against breast cancer cell lines. Apoptosis has been demonstrated to be a mechanism of the anticancer activities of Ziziphus extracts in different cell lines [83].

Table 1: Plants in the Al-Baha region that have anticancer properties

Family

Scientific name

Parts used

Target and anticancer effects

Ref.

Amaranthaceae

Chenopodium album L.

Leaves

Human breast cancer MCF-7 and MDA-MB-468 cell lines; lung cancer A549 cells

[25]

[26]

Chenopodium ambrosioides L.

Branches and leaves

Human breast cancer MCF-7 cell line

[27]

Amaranthus spinosus

Leaves

LNCaP prostate cancer cell line

[28]

Achyranthes aspera

Root

COLO-205 colon cancer cell line

[29]

Aerva javanica

Leaves

Human breast cancer MCF‑7 cell line

[30]

Aerva lanata

Fresh aerial parts

Dalton’s Ascitic Lymphoma (DAL) cell line in Swiss albino mice

[31]

Leguminosae

Acacia ehrenbergiana

Yellow flowers

Human ovarian adenocarcinoma A2780 cell line; human breast adenocarcinoma MCF7 cell line; human colon adenocarcinoma HT29 cell line

[34]

Acacia tortilis

Fresh leaves

Human liver cancer HepG2 cell line; human breast cancer MCF-7 cell line; human kidney carcinoma HEK-293 cell line

[35]

Astragalus vogelii

Aerial parts

Human colon cancer Caco-2 cell line; human lung cancer A549 cell line

[37]

Tamarindus indica

Seed kernel

Human lung cancer A549 cell line; oral epidermoid carcinoma KB cell line; human breast cancer MCF-7 cell line; Dalton's Lymphoma Ascites DLA cell line; Ehrlich Ascites Carcinoma EAC cell line

[38]

Apocynaceae

Carissa carandas L.

Leaves

Human ovarian carcinoma; human lung cancer A549 cell line; cancer cell lines MCF-7

[42]

[43]

Carissa spinarum

Stem

Colon (COLO-205 and SW-620), ovarian (IGR-OV-1 and OVCAR-5), prostate (DU-145 and PC-3), lung (A549 and Hop-62), CNS (SK-N-SH and SF-295), acute lymphoblastic leukemia (MOLT-4), and acute promyelocytic leukemia (HL-60) cell lines

[44]

 

Calotropis procera

Root

COLO-320 tumor cell line

[45]

Vitaceae

 

Cissus quadrangularis

Leaves

Ehrlich Adenocarcinoma EAC cell line; cervical cancer HeLa cell line; oral epidermoid carcinoma KB cell line; skin epithelial carcinoma A431 cell line; breast cancer MCF7 cell line; human laryngeal carcinoma HEp 2 cell line; colon carcinoma HT29 cell line; kidney epithelial cell Vero; osteosarcoma MG-63 cell line

 

[47]

[48]

 

[49]

Burseraceae

Commiphora gileadensis

Resin, stem, and leaves

Human cancer cell lines; Prostate, liver, cervical, two lymphocytic tumors, and skin cancer

[56]

[57]

[58]

Capparaceae

Capparis cartilaginea Decne.

Twigs and stem

Lung A-427 cell line; urinary bladder 5637 cell line; breast MCF-7 cell line; human hepatocellular carcinoma HepG-2 cell line; mouse fibrosarcoma WEHI-164 cell line; A549 cell line; and Madin-Darby bovine kidney MDBK cell lines

[61]

[62] [63]

Compositae

Achillea Biebersteinii

Whole flowers

AGS (human Caucasian gastric adenocarcinoma) NCBI C131 cell line; MCF7 (human breast ductal carcinoma) NCBI C135 cell line; SW742 (human colorectal adenocarcinoma) NCBI C146 cell line; SKLC6 (human lung carcinoma) NCBI C566 cell line; A375 (human melanoma cancer cell) NCBI C136 cell line; PLC/PRF/5 (human liver hepatoma) NCBI C145 cell line; HFFF (primary cell culture of human fetal foreskin fibroblast) NCBI C170 cell line

[65]

Curcurbitaceae

Citrullus colocynthis

Leaves, fruit juice, and different aerial parts

Human breast cancer MCF‑7 cell line; human colon cancer HT-29 cell line; human liver cancer HepG-2 cell line

[67]

[68]

[69] [70]

[71]

Oleaceae

Olea europaea

Leaves

Breast cancer cell lines

[74]

Papaveraceae

Argemone mexicana

Leaves and stem

Human cancer cell lines HeLa-B75, HL-60, HEP-3B, and PN-15; human lung carcinoma A549 cell line

[77]

[78] [80]

Rhamnaceae

Ziziphus spina christi

Leaves

Human breast cancer MCF‑7

[83]

 

CONCLUSION

Based on the findings of this literature review, the naturally growing plants of the Al-Baha region are rich in bioactive compounds that can be used as anticancer agents. Each of the 11 plant families (Amaranthaceae, Leguminosae, Apocynaceae, Vitaceae, Burseraceae, Capparaceae, Compositae, Curcurbitaceae, Oleaceae, Papaveraceae, and Rhamnaceae) included in this review comprised at least one genus of plants that were considered to be a source of anticancer agents. The anticancer effects of these plants differ depending on their secondary metabolites, such as phenolics, saponins, alkaloids, flavonoids, tannins, and other phytoconstituents, all of which play major roles in their cytotoxicity against carcinogenic cells. The aqueous and alcoholic extracts of 21 plant species (C. album L., C. ambrosioides L., A. spinosus, A. aspera, A. javanica. A. lanata. A. ehrenbergiana, A. tortilis, A. vogelii, T. indica, C. carandas L., C. spinarum, C. procera, C. quadrangularis, C. gileadensis, C. cartilaginea Decne., A. biebersteinii, C. colocynthis, O. europaea, A. Mexicana, and Z. spina Christi) were examined for their anticancer activities, in terms of cytotoxicity and antiproliferative effect, against different cancer cell lines. The extracts of all of the tested plants showed significant results in different cell lines, including the human lung carcinoma cell line A549; human cancer cell lines HeLa-B75, HL-60, HEP-3B, PN-15, and MCF-7; and the HepG-2, WEHI-164, MDBK, Colo-205 and SW-620, IGR-OV-1 and OVCAR-5, DU-145 and PC-3, SK-N-SH and SF-295, MOLT-4, and HL-60 cell lines. The natural growth of anticancer plants in the Al-Baha region requires further investigation to determine the specific effective components that can act as anticancer agents and to identify the best methodology to extract and use these phytochemicals. In addition, the study of a wide range of Al-Baha flora plants is necessary to record the effectiveness of local plants, which can be used as in alternative medicine against different types of cancer.

REFERENCES

  1. Réthy B, CsuporLöffler B, Zupkó I, Hajdú Z, Máthé I, Hohmann J, Rédei T, Falkay G. Antiproliferative activity of Hungarian Asteraceae species against human cancer cell lines. Part I. Phyther Res An Int J Devoted to Pharmacol Toxicol Eval Nat Prod Deriv 2007;21(12):1200–8.
  2. Rezavandi S, Masoumpoor A, Farahani AS, Nasiri M. The Relationship between Spiritual Intelligence and Depression in Parents of Children with Cancer. J. Biochem. Technol. 2018;9(3):45-50.
  3. Pandey K, Sharma PK, Dudhe R. Anticancer Activity of Parthenium hysterophorus Linn and oldenlandia corymbosa Lam by SRB Method. Open Acces Sci Reports 2012;1(6).
  4. Imran M, Bawadekji A, Nayeem N. Preparation and in Vitro Anticancer Activity Evaluation of Some Coumarin Derivatives. Pharmacophores. 2019;10(4):8-1
  5. Naik VN. Flora of Marathwada Vol. I. Amrut Prakashan, Aurangabad 1998:237–319.
  6. Nurmayanti I, Diantini A, Milanda T. Measurement of knowledge risk factors of Lung Cancer disease in salted-fish-traders at Pangandaran Indonesia. J Adv Pharm Edu Res. 2019;9(4):54-59.
  7. International Agency for Research on Cancer. World cancer report: World Health Organization. IARC Press; 2003.
  8. Al-Harbi NA, Awad NS, Alsberi HM, Abdein MA. Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Potentiality of Convolvulus Spicatus and Astragalus Vogelii. World Journal of Environmental Biosciences. 2019;8(4):69-75.
  9. Negi CS, Nautiyal S, Dasila L, Rao KS, Maikhuri RK. Ethnomedicinal plant uses in a small tribal community in a part of central Himalaya, India. J Hum Ecol 2003;14(1):23–31.
  10. Woo CC, Loo SY, Gee V, Yap CW, Sethi G, Kumar AP, Tan KH. Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-$γ$ pathway. Biochem Pharmacol 2011;82(5):464–75.
  11. Hammer KA, Carson CF, Riley T V. Antimicrobial activity of essential oils and other plant extracts. J Appl Microbiol 1999;86(6):985–90.
  12. Bariş Ö, Güllüce M, ŞAHİN F, Özer H, Kiliç H, Özkan H, Sökmen M, Özbek T. Biological activities of the essential oil and methanol extract of Achillea biebersteinii Afan.(Asteraceae). Turkish J Biol 2006;30(2):65–73.
  13. Gibbons S. An overview of plant extracts as potential therapeutics. Expert Opin Ther Pat 2003;13(4):489–97.
  14. Tanaka JCA, Da Silva CC, De Oliveira AJB, Nakamura C V, Dias Filho BP. Antibacterial activity of indole alkaloids from Aspidosperma ramiflorum. Brazilian J Med Biol Res 2006;39(3):387–91.
  15. Petrovska BB. Historical review of medicinal plants’ usage. Pharmacogn Rev 2012;6(11):1.
  16. Al-aklabi A, Al-khulaidi AW, Hussain A. Main vegetation types and plant species diversity along an altitudinal gradient of Al Baha region, Saudi Arabia. Saudi J Biol Sci 2016;23(6):687–97. https://doi.org/10.1016/j.sjbs.2002.007.
  17. Thomas J, Sivadasan M, Al-Ansari AM, Alfarhan A, El-Sheikh M, Basahi M, Alatar AA.  New generic and species records for the flora of Saudi Arabia. Saudi J Biol Sci 2014;21(5):457–64. https://doi.org/10.1016/j.sjbs.2014.07.001.
  18. Adgaba N, Alghamdi A, Sammoud R, Shenkute A, Tadesse Y, Ansari MJ, Sharma D, Hepburn C. Determining spatio-temporal distribution of bee forage species of Al-Baha region based on ground inventorying supported with GIS applications and Remote Sensed Satellite Image analysis. Saudi J Biol Sci 2017;24(5):1038–44. https://doi.org/10.1016/j.sjbs.2017.01.009.
  19. Al-Khulaidi AW, Al-Sagheer NA, Al-Turki TU, Filimban F. Inventory of Most Rare And Endangeredplant Species In Albaha Region, Saudi Arabia. IJBPAS. 2018;7(4):443-60.
  20. Howladar SM, Arabia S, Al-sodany Y, Khalik KA. Species richness of the catchment area of Al-Baha region, Saudi Arabia Species richness of the catchment area of Al-Baha region, Saudi Arabia 2015;45(5):64-91.
  21. Al-Robai SA, Mohamed HA, Howladar SM, Ahmed AA. Vegetation structure and species diversity of Wadi Turbah Zahran, Albaha area, southwestern Saudi Arabia. Ann Agric Sci 2017;62(1):61–9. https://doi.org/10.1016/j.aoas.2017.04.001.
  22. Hamayun M, Khan A, Khan MA. Common medicinal folk recipes of District Buner, NWFP, Pakistan. Ethnobot Leafl 2003;2005(1):45.
  23. Srivastav S, Singh P, Mishra G, Jha KK, Khosa RL, others. Achyranthes aspera-An important medicinal plant: A review. J Nat Prod Plant Resour 2011;1(1):1–14.
  24. Johnson JJ. Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett 2011;305(1):1–7.
  25. Khoobchandani M, Ojeswi BK, Sharma B, Srivastava MM. Chenopodium album prevents progression of cell growth and enhances cell toxicity in human breast cancer cell lines 2009;2:160–5.
  26. Zhao T, Pan HUI, Feng Y, Li H, Zhao Y. Petroleum ether extract of Chenopodium album L . prevents cell growth and induces apoptosis of human lung cancer cells 2016;12(5):3301–7. https://doi.org/10.3892/etm.2016.3765.
  27. Jia-liang W, Dan-wei M, Ya-nan W, Hong Z, Bing H, Qun L, Zhi-yan Z, Jing F. Cytotoxicity of Essential Oil of Chenopodium ambrosioides L against Human Breast Cancer MCF-7 Cells 2013;12(6):929–33.
  28. Zuhrotun A, Padjadjaran U, Diantini A, Padjadjaran U, Abdulah R, Padjadjaran U. Anticancer properties of daily-consumed vegetables Amaranthus spinosus, Ipomoea aquatica , Apium graveolens , and Manihot utilisima to LNCaP prostate cancer cell lines 2013;4(1):67-70. https://doi.org/10.4103/2229-5119.110366.
  29. Arora S, Tandon S. Achyranthes aspera Root Extracts Induce Human Colon Cancer Cell (COLO-205) Death by Triggering the Mitochondrial Apoptosis Pathway and S Phase Cell Cycle Arrest 2014;2014.
  30. Article O. Anticancer potential of leaf and leaf derived callus extracts of Aerva javanica against MCF 7 breast cancer cell line 2018;14(2):3217. https://doi.org/10.4103/0973-1482.171210.
  31. Rajesh R, Chitra K, Paarakh PM, Chidambaranathan N. Anticancer activity of aerial parts of Aerva lanata Linn Juss ex Schult against Dalton ’ s Ascitic Lymphoma 2011 Sep 1;3(3):e245-50. https://doi.org/10.1016/j.eujim.2011.05.001.
  32. Group LPW, others. A new subfamily classification of the Leguminosae based on a taxonomically comprehensive phylogeny 2017;66(1):44-77.
  33. Patel S, Shah DB, others. Phylogeny in Few Species of Leguminosae Family Based on matK Sequence. Comput Mol Biol 2014;4(4).
  34. Makeen HA, Alhazmi HA, Khalid A, Bratty M Al. Acacia ehrenbergiana Hayne grown in Jazan Region of Saudi Arabia Phytochemical, antimicrobial and cytotoxicity screening of ethanol extract of Acacia ehrenbergiana Hayne grown in Jazan Region of Saudi Arabia 2020 Apr 9;19(2):313-21.
  35. Alajmi MF, Alam P, Alqasoumi SI, Siddiqui NA, Basudan OA, Hussain A, Husain FM, Khan AA. Comparative anticancer and antimicrobial activity of aerial parts of Acacia salicina, Acacia laeta, Acacia hamulosa and Acacia tortilis grown in Saudi Arabia. Saudi Pharm J 2017;25(8):1248–52. https://doi.org/10.1016/j.jsps.2017.09.010.
  36. Carocho M, CFR Ferreira I. The role of phenolic compounds in the fight against cancer--a review. Anti-Cancer Agents Med Chem (Formerly Curr Med Chem Agents) 2013;13(8):1236–58.
  37. Sanaye M, Pagare N. Evaluation of antioxidant effect and anticancer activity against human glioblastoma (U373MG) cell lines of Murraya Koenigii. Pharmacogn J 2016;8(3).
  38. Sreelekha TT, Vijayakumar T, Ankanthil R, Vijayan KK, Nair MK. Immunomodulatory effects of a polysaccharide from Tamarindus indica. Anticancer Drugs 1993;4(2):209–12.
  39. Nazar N, Goyder DJ, Clarkson JJ, Mahmood T, Chase MW. The taxonomy and systematics of Apocynaceae: where we stand in 2012. Bot J Linn Soc 2013;171(3):482–90.
  40. Pereira AS de S, Simoes AO, Santos JUM dos. Taxonomy of Aspidosperma Mart.(Apocynaceae, Rauvolfioideae) in the State of Pará, Northern Brazil. Biota Neotrop 2016;16(2).
  41. Morales JF. Estudios en las Apocynaceae neotropicales XIX: la familia Apocynaceae s. str.(Apocynoideae, Rauvolfioideae) de Costa Rica. Darwiniana 2005:90–191.
  42. Sulaiman SF, Wong ST, Ooi KL, Yusof SR, Muhammad T, Sifzizul T. Anticancer study of Carissa carandas extracts. Proj Report USM 2008:1–6.
  43. David M, Karekalammanavar G. Spectrographic analysis and in vitro study of antibacterial, anticancer activity of aqueous ethanolic fruit extract of Carissa carandas. J Adv Sci Res 2015;6(3):10–3.
  44. Sehar I, Pal HC, Shukla S, Bhushan S, Hamid A, Gupta BD, Saxena AK. Cytotoxic evaluation and induction of mitochondria- mediated apoptosis in human leukaemia HL-60 cells by Carissa spinarum stem isolate 2011:63(8):1078-90. https://doi.org/10.1111/j.2042-7158.2011.01310.x.
  45. Smit HF, Woerdenbag HJ, Singh RH, Meulenbeld GJ, Labadie RP, Zwaving JH. {\=A}yurvedic herbal drugs with possible cytostatic activity. J Ethnopharmacol 1995;47(2):75–84.
  46. Kubitzki K, Rohwer JG, Bittrich V. The families and genera of vascular plants. vol. 1. Springer; 1990.
  47. Rajamaheswari K, Visweswaran S, Muthukumar NJ, Murugesan M, Banumathi V. A Review on Anti-cancerous potential of Cissus quadrangularis. Int J Curr Res Chem Pharm Sci 2017;4(8):1–3.
  48. Vijayalakshmi A, Kumar PR, Priyadarsini SS, Meenaxshi C. In Vitro Antioxidant and Anticancer Activity of Flavonoid Fraction from the Aerial Parts of Cissus quadrangularis Linn . against Human Breast Carcinoma Cell Lines 2013;2013.
  49. Jun W, Peng C, Wen J, Mingzhi G. Experimental study on curcumin inhibiting proliferation and invasion of human osteosarcoma cells 2017.
  50. Shah U. Cissus quadrangularis L.: phytochemicals, traditional uses and pharmacological activities-a review. Int J Pharm Pharm Sci 2011;3:41–4.
  51. Pautke C, Schieker M, Tischer T, Kolk A, Neth P, MUTSCHLER W, Milz S. Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in comparison to human osteoblasts. Anticancer Res 2004;24(6):3743–8.
  52. Suresh P, Xavier AS, Karthik VP, Punnagai K. Anticancer Activity of Cissus quadrangularis L. Methanolic Extract against MG63 Human Osteosarcoma Cells – An in-vitro Evaluation using Cytotoxicity Assay 2019;12(2):975–80.
  53. Weeks A, Daly DC, Simpson BB. The phylogenetic history and biogeography of the frankincense and myrrh family (Burseraceae) based on nuclear and chloroplast sequence data. Mol Phylogenet Evol 2005;35(1):85–101.
  54. Wood JRI, Haig-Thomas H. Handbook of the Yemen flora. Royal Botanic Gardens, Kew; 1997.
  55. Al-sieni AII, Science F, Box PO. The Antibacterial Activity Of Traditionally Used Salvadora Persica L. (Miswak) And Commiphora Gileadensis (Palsam) In Saudi Arabia 2014;11(10):23–7.
  56. Shen T, Wan W, Yuan H, Kong F, Guo H, Fan P, Lou H. Secondary metabolites from Commiphora opobalsamum and their antiproliferative effect on human prostate cancer cells. Phytochemistry 2007;68(9):1331–7.
  57. Amiel E, Ofir R, Dudai N, Soloway E, Rabinsky T, Rachmilevitch S. β -Caryophyllene , a Compound Isolated from the Biblical Balm of Gilead ( Commiphora gileadensis ), Is a Selective Apoptosis Inducer for Tumor Cell Lines 2012;2012. https://doi.org/10.1155/2012/872394.
  58. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144(5):646–74.
  59. Wineman E, Douglas I, Wineman V, Sharova K, Jaspars M, Meshner S, Bentwich Z, Cohen G, Shtevi A. Commiphora gileadensis sap extract induces cell cycle-dependent death in immortalized keratinocytes and human dermoid carcinoma cells. Perspect Med 2015;5(4):199–206. https://doi.org/10.1016/j.hermed.2015.08.001.
  60. Mabberley DJ. The plant-book: a portable dictionary of the vascular plants. Cambridge university press; 1997.
  61. Mothana RA, Lindequist U, Gruenert R, Bednarski PJ. Studies of the in vitro anticancer, antimicrobial and antioxidant potentials of selected Yemeni medicinal plants from the island Soqotra. BMC Complement Altern Med 2009;9(1):7.
  62. Esmaeili S, Hamzeloo-Moghadam M, Ghaffari S, Mosaddegh M. Cytotoxic activity screening of some medicinal plants from south of Iran. Res J Pharmacogn 2014;1(4):19–25.
  63. Igbe I, Ching FP, Eromon A. Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation. Acta Pol Pharm 2010;67(1):81–5.
  64. Lundberg J, Bremer K. A phylogenetic study of the order Asterales using one morphological and three molecular data sets. Int J Plant Sci 2003;164(4):553–78.
  65. Ghavami G, Sardari S, Shokrgozar MA. Anticancerous potentials of Achillea species against selected cell lines 2010;4(22):2411–7. https://doi.org/10.5897/JMPR10.560.
  66. Rubatzky VE, Yamaguchi M. World vegetables: principles, production, and nutritive values. Springer Science & Business Media; 2012.
  67. Tannin-spitz T, Grossman S, Dovrat S, Gottlieb HE, Bergman M. Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells 2007;73(1):56– https://doi.org/10.1016/j.bcp.2006.09.012.
  68. Marzouk Z, Marzouk B, Mahjoub MA, Haloui E, Mighri Z, Aouni M, Fenina N. Screening of the antioxidant and the free radical scavenging potential of Tunisian Citrullus colocynthis Schrad. from Mednine. J Food, Agric Environ 2010;8(2):261–5.
  69. Mukherjee A, Patil SD. Effects of alkaloid rich extract of Citrullus colocynthis fruit on Artemia salina and human cancerous (MCF-7 and HEPG-2) cells. J PharmaSciTech 2012;1(2):15–9.
  70. Tavakkol Afshari J, Rakhshandeh H, Zamani AR, Mahdavi Shahri N, Ghazezadeh L, Norozi M. Cytotoxicity effects of Citrullus colocynthis on Hep2 and L929 cell lines. Hakim 2005;8(2):47–54.
  71. Davoodi R, Najafi SH, Mazaheri M, others. Effect of hydro alcoholic extract of citrullus colocynthis fruit on caspase 3 gene expression in MCF-7 breast cancer cell line. SSU_Journals 2015;23(5):508–18.
  72. Kalwij JM. Review of ‘The Plant List, a working list of all plant species.’ J Veg Sci 2012;23(5):998–1002.
  73. Altemimi AB. A study of the protective properties of Iraqi olive leaves against oxidation and pathogenic bacteria in food applications. Antioxidants 2017;6(2):34.
  74. De Matteis V, Rizzello L, Ingrosso C, Liatsi-douvitsa E. Cultivar-Dependent Anticancer and Antibacterial Properties of Silver Nanoparticles Synthesized Using Leaves of Different Olea Europaea Trees. Nanomaterials. 2019 Nov;9(11):1544.
  75. Judd WS, Campbell CS, Kellogg EA, Stevens PF, Donoghue MJ. Plant systematics: a phylogenetic approach. Ecol Mediterr 1999;25(2):215.
  76. Björk CR. Taxonomy of Papaver sect. Meconella (Papaveraceae) in British Columbia 2019.
  77. Gacche RN, Shaikh RU, Pund MM. In vitro evaluation of anticancer and antimicrobial activity of selected medicinal plants from Ayurveda. Asian J Trad Med. 2011;6(3):1-7.
  78. Brahmachari, G., Gorai, D., Roy, R. Argemone mexicana: chemical and pharmacological aspects. Revista Brasileira de Farmacognosia. 2013;23(3), 559-567.
  79. Brahmachari G, Gorai D, Roy R. Argemone mexicana: chemical and pharmacological aspects. Revista Brasileira de Farmacognosia. 2013 Jun;23(3):559-67. https://doi.org/10.1590/S0102-695X2013005000021.
  80. More N V, Kharat AS. Antifungal and Anticancer Potential of Argemone mexicana L. Medicines. 2016;3:28
  81. Richardson JE, Fay MF, Cronk QCB, Bowman D, Chase MW. A phylogenetic analysis of Rhamnaceae using rbcL and trnL-F plastid DNA sequences. Am J Bot 2000;87(9):1309–24.
  82. Burge DO, Erwin DM, Islam MB, Kellermann J, Kembel SW, Wilken DH, Manos PS. Diversification of Ceanothus (Rhamnaceae) in the California Floristic Province. Int J Plant Sci 2011;172(9):1137–64.
  83. Vahedi F, Najafi MF, Bozari K. Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology 2008;56(2):105–11.