Anti-proliferative, genotoxic and cytotoxic effects of phytochemicals isolated from Anatolian medicinal plants

The potential of natural products in cancer prevention and treatment has received worldwide interest in recent years from the nutraceutical and pharmaceutical industry point of view. Medicinal plants have been traditionally used as they exhibit a wide range of therapeutic effects due to their phytoconstituents which play an active role against oxidative stress-associated diseases such as cancer. They may block or suppress multistage carcinogenesis mainly through mechanistic regulation of the myriad of deregulated cellular pathways. Bioactive constituents isolated from different plants have been shown to induce reversal of drug resistance, restoration of apoptosis, inhibition of cell proliferation and stimulation of the immune system, etc. These phytochemicals such as terpenoids, flavonoids, phenolic acids, carotenoids, alkaloids, tannins, anthraquinones, and saponins can be present in any of the plant parts like root, stem, leaves, bark, seed, flower, and fruit which produce a definite physiological response in the organism. Turkish flora is a rich reservoir of wide-ranging bioactive chemicals having premium pharmacological importance. This review provides an overview of the anticancer properties of various Turkish medicinal plant species against different type of cancers via anti-proliferative, genotoxic and cytotoxic effects.


Introduction
Cancer is the second leading cause of death worldwide. According to the report of the International Agency for Research on Cancer of the World Health Organization in 2014, the most prevalent cancer was lung cancer in 2012 followed by breast cancer, colon cancer, and prostate cancer (1). Because of rapidly developing resistance against modern clinical drugs and significant off-target effects, botanicals offer a precious reservoir of pharmacologically effective products to inhibit and/or prevent cancer. Eliminating toxicity issues of current drugs, edible phytochemicals are considered to be an inexpensive and accessible approach in chemoprevention. Nearly, 80% of all drugs approved by the FDA during the last three decades for cancer therapy are either natural products per se or are based thereon, or mimicked natural products in one form or another (2).
Many clinical trials on the use of nutritional supplements and modified diets to prevent cancer are on-going. Medicinal plants are utilized both internally like herbal teas and externally such as poultice, decoction, ointment and other herbal formulations in order to cure a broad spectrum of ailments (3,4). The relevant biological activities are attributed to a vast array of phytochemicals ('phyto' is from the Greek word meaning plant)-the bioactive non-nutrient plant compounds. More than 10,000 phytochemicals have been identified to date (5). The most consistent chemoprotective effects were reported for higher levels (dietary intake, serum, plasma, or urinary metabolites) of β-carotene and renal cell cancer, flavonoids and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer (6).
Carcinogenesis is generally recognized as a multistep process in which distinct molecular and cellular alterations occur (7). There are many difficulties associated with its treatment, the most common of which include drug resistance, toxicity and the low specificity of currently available cytotoxic drugs (8). Phytochemicals exert anticancer effects through modulation of cellu-lar and molecular events relying on antioxidant and anti-inflammatory properties (5,9). Furthermore, phytochemicals have been shown to restore apoptosis in drug-resistant cancer cells, downregulate oncogenes, upregulate tumor-suppressor genes, as well as inhibit angiogenesis and metastatic spread (7).
The anticancer effects of medicinal plants have been recognized for centuries. The United States National Cancer Institute reported that about 3,000 plant species have demonstrated reproducible anticancer activity among screened approximately 35,000 species (10). With a rich diversity of plants where more than 12,000 taxa are growing, Turkey is the richest among the Mediterranean, European and neighboring countries (11). Endemic plants are represented as one third of the native taxa (12). The most frequently employed plant families in traditional Turkish ethnic medicine are the Lamiaceae, Rosaceae and Asteraceae families (3). Identification of new sources of phytochemicals is an essential step in improving the translation of these laboratory findings to clinically efficient drugs. As can be seen in Table 1, the dominant families that were subjected in cancer studies are Lamiaceae, Liliaceae, Rosaceae, Asteraceae, Scrophulariaceae, Rubiaceae, Moraceae, Hypericaceae, and Ericaceae. Both endemic and non-endemic Turkish medicinal plants belonging to a variety of plant families and their phytochemicals responsible for anticancer effects on various cell lines and animal models were highlighted in this review.

Apiaceae
The family Apiaceae comprises about 170 aromatic plant species occurring from central Asia westward to northern Africa that is well-known in folk medicine for the treatment of various organ disorders (13). The plant family Apiaceae is known to produce a set of unusual fatty acids in the seed oils in which petroselinic acid as the predominant constituent (14). Essential oils from Italian Eryngium rich in sesquiterpene hydrocarbons, with germacrene D as the major compound, were found to be highly cytotoxic against tumor cells (15). Subgenus Eryngium L. is centered in the Mediterranean type climate and Turkey is an eminent region for the genus (16). Anti-inflammatory and antinociceptive activity of Turkish Eryngium species have been reported (17). Among extracts derived from 11 different plant species grown in Turkey, methanolic Eryngium campestre extract and aqueous Asarum europaeum (Aristolochiaceae) extract obtained from Bolu province indicated by far strongest tumor inhibition rates, 86% and 100%, respectively (18). Triterpene saponins, coumarin derivatives, monoterpene glycosides and flavonoids comprise the phytochemical composition of E. campestre (19).
A famous traditional Chinese Medicine, Radix Bupleuri, originating from herbs belong to Bupleurum L. is a widely used herbal drug in Asia to treat of a number of diseases including common cold with fever, influenza, hepatitis, malaria and menoxenia for more than 2000 years (20). The anti-proliferative activity of Bupleurum species has been linked to the presence of different lignans whereas anti-inflammatory, hepatoprotective and immunomodulatory activities has been attributed to saikosaponins (21). Kars, Akin, & Saraccedil (2012) investigated Turkish endemic Bupleurum root extracts against human breast carcinoma cells. B. turcicum and B. pauciradiatum root extracts were more toxic to the MCF-7/Pac cell line than the root extracts of other three species. B. turcium root extract had the highest free radical scavenging activity although B. lycaonicum root extract has about 1.5-fold more total phenolic content with respect to others. Moreover, higher saikosaponin A, saikosaponin D and isoquercitrin contents of the root extracts were found in comparison to podophyllotoxin, catechin and quercetin contents (22).

Asteraceae
The genus Centaurea belonging to the Asteraceae family comprises nearly about 600 species through the World and mostly distributed in the Mediterranean region and Western Asia (23). Turkish flora is one of the gene centers of Centaurea having nearly two hundred species many of which (> 60%) are endemic (24). In Anatolian folk medicine, some Centaurea species have been employed as herbal remedies in the treatment of fever, hemorrhoids, diabetes, and peptic ulcer (25,26). Secondary metabolites present in this genus, revealed in previous pharmacological studies, including sesquiterpene lactones (27,28), acetylenic compounds (29), and flavonoids (30).
An endemic Centaurea species, C. drabifolia Sibth. & Sm. subsp. detonsa collected from the Central Anatolia region of Turkey, has been reported to contain acylated guaiane sesquiterpenes (33). Antiproliferative activity of an apolar organic extract from aerial parts was shown on two cancer cell lines, namely acute lymphoblastic leukemia and its multidrug-resistant subline likely attributed to aguerin B and cynaropicrin contents (33). Similarly, aerial parts of endemic Centaurea fenzlii Reichardt collected from East Anatolian region indicated significant cytotoxic effects on the MCF-7 breast cancer cell line (34). Hispidulin was reported as the main component (34). In the study of Sen and coworkers (2015), chloroform and methanol extracts of another endemic Centaurea species, C. kilaea Boiss. showed the highest antitumor activity with IC 50 of 73.92 and 70.11 μg/mL, respectively against prostate carcinoma in vitro (35).

Ericaceae
Rhododendron luteum and Rhododendron ponticum, which are non-evergreen short trees with green leaves and have flowers of different colors and usually used as a decoration plants, grow naturally in Turkey, especially in eastern Black Sea Region (18,36). Extracts of the Rhododendron species are composed of several bioac-that some of them produce a high amount of essential oil that enables them to survive the hot summer season. It consists of approximately 236 genera and 6,900 to 7,200 species (50). Many prevalent culinary herbs, such as basil, lavander, marjoram, mint, basil, oregano, perilla, rosemary, sage, skullcap, and thyme are members of this family (51). Besides its great economic importance, this family contributes significantly to the endemic flora of Greece and Turkey (52). In Lamiaceae species, essential oils, hydroxycinnamic acids and flavonoids were found as the major bioactive constituents (53).
Essential oils are the subtle, highly concentrated, aromatic, and volatile liquids. These are extracted from the flowers, seeds, leaves, stems, bark, and roots of plants, usually through steam or hydro-distillation. These natural oils are mixtures of complex and volatile compounds that are synthesized by aromatic plants as secondary metabolites (13). The composition of Origanum vulgare essential oil from distinct geographical origins is predominantly described by carvacrol and thymol as the major constituents. Phenolic acids and flavonoids are also present substantially (54). Anticancer effects of various Oreganum species from different origins have been well documented in the literature (55)(56)(57)(58)(59). Essential oil of Origanum vulgare L. ssp. viride (Boiss.) Hayek that was collected from Black Sea region of Turkey and carrying anti-proliferative activity was dominated by caryophyllene oxide, while sabinene and eucalyptol were the main monoterpenoid volatiles (60). It has been shown that luteolin 7-O-glucuronide and luteolin 7-O-xyloside present in O. vulgare L. ssp. vulgare have antimutagenic properties (61). On the other hand, the essential oils from Turkish O. onites containing linalool as the most abundant component have been reported to possess higher membrane-protective effects than thymol and carvacrol (62).
Another Lamiaceae genus containing thymol and carvacrol is Thymus L. is represented by 38 species and 64 taxa, 24 of which are endemic in Turkey and the East Aegean Islands (63). There are several chemotypes of Thymus vulgaris. Rosmarinic acid, luteolin, apigenin, eriodictyol, and some methylated flavones were also reported in thyme (64,65). Essential oil of Turkish Thymus revolutus Celak, an endemic species, has γ-terpinene and p-cymene as major constituents (66). In the study of Özkan and Erdoğan (2017), the cytotoxic effects of Thymus revolutus Celak have been evaluated against lung cancer and epidermoid carcinoma cells. Occurrence of membrane lipid peroxidation and oxidation of DNA, due to elevated levels of malondialdehyde and 8-hydroxy-2′-deoxyguanosine have been indicated (67). In addition, a potent proliferative activity has been reported for hexane and water extracts of Thymus spathulifolius, an endemic ethnomedicinal plant from Sivas Province (68).

Liliaceae
Species belonging to the Liliaceae have been a focus for phytochemists since they contain structurally complex and biologically fascinating steroidal alkaloids. The Liliaceae family consists of more than 3500 species worldwide (69). Colchicum L. (Liliaceae) is represented by 35 species, of which 14 are endemic and known as tive compounds (Table 1), but they also contain "grayanotoxins", a class of terpenoids that exhibit phytotoxic effects, and for this reason the usage of this genus in traditional medicine is limited (37). On the other hand, grayanotoxins exhibit cytotoxic effects on cancer cells. Recently, Bilir and co-workers demonstrated the dosedependent cytotoxic effect of Rhododendron ponticum L. floral extract with grayanotoxin-I and grayanotoxin-III on brain tumors. Removal of grayanotoxins during extraction process is a convenient option for eliminating the side effects of Rhododendron species (38). Antiproliferative activity of Rhododendron luteum on colon and liver cancer cells was reported (39). More importantly, it was pointed out that the Rhododendron luteum floral extract exhibited selective cytotoxicity against colon and liver cancer cells.

Fabaceae
Astragalus L. is a member of the Fabaceae family which containing up to 3000 species (40). The aqueous extract of Astragalus roots are traditionally used for treatment of nephritis, diabetes, leukemia and woundhealing in both Anatolia and Chinese medicine (41,42). Astragalus is the largest genus in Turkey where it is represented by 439 species and 204 of them are endemic (43). One of the endemic species is Astragalus chrysochlorus that growing in 32°-36° meridian of southern Anatolia (44). The cytotoxic effects of the ethyl acetate extract of Astragalus chrysochlorus roots on cervix cancer cells was reported (45). It was also indicated that there was a significant change especially on antiapoptotic genes due to the presence of the root extract. Rebalancing pro-and anti-apoptotic proteins through upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins is necessary to induce apoptosis in drug-resistant cancer cells. Özbek et al. (2008) studied on the antimutagenic effects of methanol extract of Astragalus L. species growing in the eastern Anatolia region of Turkey. They indicated that Astragalus extracts can be considered to be protective agents against cancer, as they showed antimutagenic effects (46).

Hypericaceae
Members of the Hypericum genus have been used as traditional medicinal plant for hundreds of years. The genus contains approximately 400 species that grow widely at temperate region of the world, where 89 Hypericum species in present the flora of Turkey which 43 are endemic (47). Ari and co-workers (2017) investigated the anti-proliferation and cytotoxic activities of the crude methanol extracts of Hypericum olympicum L. and H. adenotrichum on brain and liver cancer cells. Their findings showed that, these extracts have potential anti-growth activity against brain and liver cancer cells in a dose dependent manner, moreover, induce cell death via necrosis (48).

Lamiaceae
The Lamiaceae family, also known as Labiatae, are herbs or shrubs often with an aromatic smell (49). They are common in the Mediterranean countries for the fact 'Acicigdem' in Turkey (70). Tropolone alkaloid components of the distinct species belonging to the genus Colchicum were dissimilar according to the different regions and growth stages (71). Colchicine, the main alkaloid of genus Colchium, is an antitumor agent that is classified as a mitotic inhibitor (72). An effective in-vitro antitumor activity on cervical carcinoma cells has been indicated for Turkish Colchicum sanguicolle methanolic extract with IC 50 values of 0.01 mg/mL and 0.001 mg/mL at 48 hrs for HeLa and C4-I cell lines, respectively (73). In addition, an endemic species, Colchicum sanguicolle K.M. Perss, revealed significant selective toxicity against the HeLa cell line whereas indicated low cytotoxicity on the Vero cell line (74). The degree of selectivity is defined by its selectivity index (SI = IC50 normal cell/IC50 cancer cell) (75). Plants of the genus Asphodeline have been traditionally used as medicinal plants in various parts of the world. The genus contains 20 taxa, 12 of which are endemic in Turkey (76). A number of Asphodeline species are used to alleviate warts and heal wounds and to treat earaches and hemorrhoids in Turkish folk medicine. Moreover, species of A. cilicica, A. damascena, A. globifera, A. lutea and A. taurica are consumed as salad vegetables in different regions (77). In the study of Lazarova and coworkers (2015), methanolic extracts of A. lutea roots from Turkish and Bulgarian origins were assessed for their ability to regulate the growth of the breast cancer cell line MCF-7 and the noncancerous breast epithelial cell line MCF-10A and their anti-proliferative effect were reported. A naphthalene derivative (2-acetyl-1,8-dimethoxy-3-methylnaphthalene) was the major compound in Bulgarian accession while Turkish accession had caffeic acid as the most abundant (78).
Eremurus spectabilis (serish -common name and ciris -local name) belongs to the family Liliaceae and is geographically distributed in the region of South Asia and Central Asia, including Iran, West Pakistan, Afghanistan, Iraq, Palestine, Lebanon, Syria, Caucasus and Turkey (79). Growing in spring and localized in the east of Turkey, Eremurus species used in folk medicine to cure ailments such as hemorrhoids and diabetes, and also used as antihypertensive and antidysuria agents (80). Recently, anticancer activity of Turkish E. spectabilis leaves and roots originating from Bingol Province has been reported against prostate cancer cells. Acetone, ethanol and water extracts activated mitochondrially-triggered apoptosis in PC-3 cells by up-regulation of Bax and caspase-3 and down-regulation of Bcl-2 mRNA (81).
Urginea maritima (L.) Baker (Liliaceae) is a cardiac glycoside-producing native Mediterranean medicinal plant, commonly known as squill (82). In traditional medicine, it has been used for many centuries due to its for powerful digitalis-like cardiac effect (83), and is also used as a diuretic and heart stimulant (84). Bulbs of Urginea indica have been reported with potent in-vivo antitumor activity against growth of an ascites tumor (85). A bioactive bufadienolide that was subsequently shown to be proscillaridin A has been isolated from alcoholic Egyptian U. maritima extracts (82). Turkish Urginea maritima (L.) Baker has been reported to be a strong candidate for drug development against solid tumors. The bulb extract (1 μg/mL) was found more cytotoxic than cisplatin (1 μg/mL), gemcitabine (1 nm/mL), or the leaf extract (1 μg/mL). Hence, the authors claimed that U. maritima extracts induced more cytotoxicity than standard chemotherapeutics in the A549 non-small cell lung cancer cell line (86).
The genus Allium belonging to the family Liliaceae includes approximately 500 species all over the world (87). Allium L. is one of the largest genera in the Turkish flora. The total number known from Turkey is 190 of which 75 taxa are endemic (88). The members of this genus have been reported to possess antitumoral (89), antimicrobial (90), antioxidant (91), antiviral (92), antidiabetic (93) properties. The potential use of Allium species as anti-cancer agents has been reviewed previously (94,95). A well-known plant is garlic (Allium sativum) having a place among oldest cultivated plants in Middle and West Asia (96). A lower prevalence of cancer has been indicated countries where garlic is traditionally consumed in higher amounts (97). It has sulfur-containing phytochemicals such as diallyl disulfide which has been found as highly effective in affording protection against cancer in animal and clinical studies (98,99). The antiproliferative properties Allium sivasicum collected from Sivas region was investigated on breast cancer cell lines, namely MCF-7 (IC 50= 21 ± 1,4 µg/mL), MDA-MB-468 (IC 50= 22 ± 1,4 µg/mL) and MDA-MB-231 (IC 50= 24 ± 1,3 µg/mL). In addition, the aqueous extract of A. sivasicum exhibited mean tumor volume inhibition ratio of 38% in the treated group in comparison with the untreated in female albino Wistar rats (89).

Moraceae
Morus rubra L. and Morus nigra L. are the most extensive Morus species that belongs to the family Moraceae. These species have been cultivated in Europe and Asia since pre-Roman times (100,101). The deepcolored Morus fruits, commonly known as mulberries, are a rich source of phenolic compounds such as flavonoids, anthocyanins and carotenoids (102). Since the Morus species contain various phenolic content in high amounts, the fruits exhibit antimicrobial, antioxidant, antidiabetic, anti-HIV, anti-inflammatory, hypolipidemic, hepatoprotective, antiobesity, neuroprotective and anticancer activities (102)(103)(104)(105)(106). Proapoptotic and antiproliferative properties of Morus nigra dimethyl sulfoxide extract on prostate cancer cells was evaluated. Researchers reported that Morus nigra extract arrested the cell cycle of prostate cancer cells at the G1 phase, therefore inducing apoptosis by increased caspase activity and reduced mitochondrial membrane potential of prostate cancer cells (107). A similar proapoptotic and antiproliferative mechanism was also observed in the effect of Morus rubra extract on colon cancer cells, which is summarized in Table 1 (108). On the other hand, to understand in more detail the exact anticancer mechanism, phytochemical analyses should be carried out in addition to in vivo biological activity experiments (107,108).

Rosaceae
The family Rosaceae is a remarkable taxon with res-Cell Mol Biol (Noisy le Grand) 2020 | Volume 66 | Issue 4 Kadriye Nur Kasapoğlu et al. pect to systematic biology (109). It is diversified particularly in the northern hemisphere and comprises more than 100 genera and 3000 species (110). Numerous well-known and beloved species of economic importance. Temperate zone members of the family are well known for edible fruits (111) in addition to some timber crops and medicinals (112). For example, cherry, apricot, almond, peach, apple, pear, plum, hawthorn, strawberry, blackberry, and rosehip belong to Rosaceae (112). When antioxidant activities of infusions prepared form 70 medicinal plants belonging to different taxa were compared, leaves of raspberry, blackberry, and strawberry were among eleven of the most effective plants (113).
Rosa canina L. from in Rosaceae has long been used for medicinal purposes. Turkey has one of the most substantial native populations of rose species with about 25% of rose species growing in Turkey (114). Phytochemicals such as phenolic acids, proanthocyanidins, tannins, flavonoids, pentacyclic triterpenes have been reported (115). R. canina is traditionally used to treat of colds, asthma, hemorrhoids, infections, chronic pains, arthritis, and inflammatory diseases in both Western and Asian countries (114)(115)(116). Being also a good source of vitamin C, it has been reported that only polyphenols contribute to its antiproliferative activity (117). The fruits have recently been suggested as a source of potent novel phytochemical anticancer agents. It was reported that R. canina extract reduced mitochondrial membrane potential and the expression of telomerase in human colon cancer cells; it induced apoptosis and cell cycle arrest at the S phase. Moreover, selective cytotoxic effect of the extracts on colon cancer cells was highlighted (116).
Besides the anticancer properties of natural extracts, recent studies showed that, natural extracts can be more effective therapeutic agents against tumors than standard chemotherapeutic candidates (118). It was demonstrated that the methanol extract of Crataegus monogyna (Rosaceae) exhibited better antiproliferative activity than standard chemotherapeutics 5-flurouracil and cisplatin on brain tumors and cervical cancer cells (119). Furthermore, the natural extracts can be added to the standard anticancer drugs for increasing their treatment effectiveness and reducing their side effects. Aydın et al.
(2016) showed that high concentration of Prunus laurocerasus aqueous fruit extract destroyed the cellular membrane of tumor cells. Furthermore, they indicated that when the P. laurocerasus aqueous fruit extract did not show effective anticancer properties, it can still be a potential adjuvant therapy to current chemotherapeutic agents. For this reason, adding the P. laurocerasus extract to the chemotherapeutic formulation has been suggested. The fatty acid-rich bioactive components of Turkish cherry laurel fruit extracts have been reported to be responsible for the chemoprotective effect against HT29, HeLa, C6 and Vero cell lines (118). Furthermore, aqueous ethanolic extracts prepared from cherry pulp have been evaluated for their anti-cancer activity. The antiproliferative activity of Prunus cerasus was shown on breast cancer cells. The extract induced apoptosis and reduced the asymmetric dimethylarginine concentration. Therefore, P. cerasus extract may be considered as a novel prophylactic therapeutic agent for breast can-cer (120).

Rubiaceae
Galium aparine L. and Morinda citrifolia L. belong to the Rubiaceae family, which are commonly used in folk medicine for the treatment of wounds, fever and hypertension (121,122). The previous studies showed that these plants contain several anticarcinogenic compounds, as they can be a part of cancer treatment strategies (Table 1). Galium aparine grows throughout Anatolia and is a typical climbing plant (123). Atmaca and co-workers (2016) identified 14 major phytochemicals and 34 volatile compounds in the ethanol extract of the aerial parts of G. aparine. They reported that the extract induced apoptosis of breast cancer cells, while it did not show any negative effects on normal breast epithelial cells. More importantly, they assumed that the G. aparine extract may enable the killing of apoptosis resistant breast cancer cells (124). In another study, the anticarcinogenic effect of Morinda citrifolia was investigated via in vivo experiments. It was found that the fruit of M. citrifolia induces apoptosis of breast cancer cells. Therefore, it can be used the treatment of breast cancer either on its own or in combination with doxorubicin, which is a most commonly used chemotherapeutic for breast cancer (121).

Scrophulariaceae
The Scrophulariaceae contains more than 220 genera, where Scrophularia spp. and Verbascum L. spp. commonly grow in Turkey. In the traditional practices, these plants are used for the treatment of scabies, eczema, psoriasis, hemorrhoids, rheumatic pain, superficial fungal infections, wounds and diarrhea. (125,126). The major bioactive compounds in the Scrophulariaceae plants are of sugar esters, iridoid glycosides, oleanane type triterpenoids, flavonoids, polysaccharides, saponins, steroids and alkaloids (127,128). Anti-inflammatory and anti-neoplastic effects of Scrophularia spp., have been reported. Moreover, it has been shown that the methanol extract of Scrophularia spp. induced apoptosis in breast cancer cells as well as exhibited strong antiproliferative properties (129). Verbascum L. is another genus that belongs to Scrophulariaceae family, where the methanol extract of V. pycnostachyum has selective cytotoxic effects on cervical and ovarian cancer cells (130).

Urticaceae
In traditional medicine, both roots and leaves of Urtica diocia are used as an adjuvant remedy in the treatment of several diseases especially for cancer therapy (131). The bioactive compounds of U. diocia leaves have been shown to inhibit the genetic transcription factor which activates the tumor necrosis factor-α (TNF-α) (132). The anticancer properties of U. diocia have also been demonstrated by the inhibitory activity on adenosine deaminase. The inhibition of adenosine deaminase in cancerous gastric tissues was reported for the aqueous extract (133). In an in-vivo study, rats that had been exposed to the chemical carcinogen trichloroacetic Cell Mol Biol (Noisy le Grand) 2020 | Volume 66 | Issue 4 Kadriye Nur Kasapoğlu et al. acid (TCA) were fed a beverage of U. diocia for 50 days and investigated the protective effects of the beverage. They observed that since the U. diocia contains strong antioxidant compounds (Table 1), the oxidative stress, which is induced by TCA, was remarkably reduced in the U. dioica fed rats. Thus, they reported that U. diocia beverage can be thought as a potential cancer preventive supplement since has a protective effect against oxidative injury (134).

Concluding Remarks
It is exciting to note that Anatolian plants provide a rich source of whole extracts and isolated bioactive phytochemicals of pharmacological importance. However, much of the available data have been derived through preliminary findings. Future studies are needed with in-depth and detailed research with special focus on regulation of deregulated pathways by natural products obtained from Turkish flora in different cancers to realistically evaluate potential of bioactive components.