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Akhtar K, Baloch A W, Kurmashvili A. Phytochemicals as Safe Agents for Prevention of Cancer: Recent Advances in Cancer Therapy . GMJ Medicine. 2018; 2 (1) :65-71
URL: http://gmjpress.de/article-1-42-en.html
1- Livestock & Dairy Development Department Balochistan, Quetta, Pakistan
2- Department of Intelligent Medicine, International Center for Intelligent Research, Tbilisi, Georgia
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Cancer has been known as one of the genetic disorder [1] and also as second cause for death in developed countries [2]. The estimations have been shown that cancer is almost reason for 13% of total deaths and its global distribution is variable in the different populations due to aging and growth of the world population [3, 4]. It has been known by 100 types of cancer and classified by their cells [5]. I t has been reported that 14.1 million new patient with cancer exception those with skin cancer other than melanoma [6]. It has been estimated to be 26 million new case of cancer and 17 million cancer death yearly [7]. Despite significant progresses, cancer has been yet known as an aggressive killer in all over worldwide. Surgery, chemotherapy and radiotherapy are common procedures for treatment of cancer [8]. Such treatments have limitations such as side effects including fatigue, pain, diarrhea, nausea, vomiting, and hair loss [9] and could be also caused gradual resistance of cancer cells against treatment [10]. It has been shown that by half of cancer enduring in the United States exploit components derived from the various parts of plants or nutrients, singly and as adjuvant treatment in alongside chemotherapy and/or radiation therapy [11-13]. From long years ago, natural herbal medicines have been applied in order to prevention and/or treatment of different diseases [14]. Phytochemicals makes them appropriate for food consumers [15-17]. Studies have approved anticancer activities of phytochemicals [18-22]. Natural compounds of plants belonging to different groups including alkaloids, diterpenes, diterpenoquinone, purine-based compounds, lactonicsesquiterpene, peptides, cyclicdepsipeptide, proteins, macrocyclicpolyethers, etc [23]. Some phytochemicals have been known to have anticancer activity and on the other hand modern medicine lacks effective drugs against certain types of cancers, including metastatic pancreatic adenocarcinoma and castration-resistant prostate cancer [23]. In this review article, we have described the use of phytochemicals for prevention of cancer and review the previous published studies and present implications for it.
A brief of phytochemicals
The Greek term “phyto” in phytochemicals is originated from plant [24, 25]. Phytochemicals has been defined as bioactive, non-nutrient, and naturally present in plant compounds which are found especially in fruits, vegetables, and whole grains. It has been estimated to be 5000 especial phytochemicals in grains, fruits and vegetables but a large number are not yet known and must be known before understanding their health advantages in whole foods [26]. Phytochemicals present in plant substances have increased interest among researchers, food production and also for pharmaceutical industry and/or for their uses in the prevention of human health. They are divided into different groups including polyphenols, organosulfur compounds, carotenoids, alkaloids, and nitrogen-containing compounds [27]. Some phytochemicals has also been known as effectors of biologic processes and also have ability for influencing on disease risk through complementary and overlapping mechanisms [27]. Phytochemicals can penetrate and delay promotion multistep carcinogenesis [29] and also postpone the progression of precancerous cells into the malignant ones [29, 30].
The phenolics as secondary metabolites are broadly in plants especially in fruits [31]. They are known to have 1, 2 and/or more aromatic rings [32]. They have antioxidant properties and prevent against cancers. Their profitability could be attributed to their regular consumption and bioavailability [33]. They are precursors for flavonoids and tannins [34, 35]. Hydroxycinnamic acids and their derivatives in fruits and vegetables are resulted from p-coumaric acid (PCA), caffeic acid (CA), and ferulic acid (FA) [36]. Flavonoids are known as main class of phenolic structures that have antioxidant activity [37]. Such phytochemicals are connected in order to decrease the risk of main chronic diseases and largely identified in fruits, vegetables, and other plant foods [38]. They are divided into flavonols, flavones, flavanols (catechins), flavanones, anthocyanidins, and isoflavonoids that have one heterocyclic C ring [39]. The chemical structure of flavonoids relies on their functional group, rate of hydroxylation, other substitutions and conjugations, and rate of polymerization [40]. Functional hydroxyl groups present in flavonoids act in antioxidant activity through scavenging free radicals and/or through chelating metal ions [41, 42]. Flavonoids are placed in the nucleus of mesophyll cells and inside centers of reactive oxygen species group. Some possible mechanisms have been suggested for the effect of flavonoids in the initiation and encourage the stages of the carcinogenicity such as effects on development and hormonal activities, including: (1) Down regulation of mutant p53 protein, (2) Stopping cell cycle arrest, (3) Prevention of tyrosine kinase activity, heat shock proteins and expression of Ras proteins [43]. Organosulfur structures are known as organic structures that could be identified by their sulfur having functional groups [44]. Daily consumption of organosulfur components could improve bioactive characteristics particularly in relation with cardiovascular health [45].Some organosulfur components were evaluated based on their ability for prevention carcinogenesis promoted through N-nitrosodiethylamine and the best was observed in diallyl disulfide [46]. Some organosulfur structures in Allium genus have been shown anti-cancer activity [47].

Carotenoids are known as natural pigments which have received attentions. More than 600 different carotenoids have been recognized in nature. They may be originated from plants, microorganisms, and/or animals. They have a skeleton of isoprene units containing 40-carbon [48]. Carotenoids can react with free radicals and produce radicals [49]. The α-carotene has been known to have strong protective factor. The β-carotene present in green leafy vegetables act as an antioxidant, but it has prooxidant effects in high levels and particularly in high oxygen tension [2]. Antioxidant activity of carotenoids could be attributed to antioxidant activity.

Alkaloids are known class of ring compounds nitrogen having organic compounds which have a broad range of anticancer properties [50]. Such structures have activity in prevention of cancer by inhibition of enzyme to poisomerase activity that is involved in DNA imitation, induction of apoptosis and gene expression of p53 gene [51, 52]. Alkaloids have similar structure neurotransmitters in the central nervous system of human beings. With regards to alkaloids and research in relation with their role for treatment of wild propagation of cells, they have been used as an efficient chemo preventive substance [53, 54]. Amaryllidaceae alkaloids, betalain alkaloids, diterpenoid alkaloids, indole alkaloids, isoquinoline alkaloids, lycopodium alkaloids, monoterpene and sesquiterpene alkaloids, peptide alkaloids, pyrrolidine and piperidine alkaloids, pyrrolizidine alkaloids, quinoline alkaloids, quinolizidine alkaloids, steroidal alkaloids, tropane alkaloids, and miscellaneous alkaloids have been known as the major class of Alkaloids [47]. Catharanthus alkaloids have been used as adjuvant treatment for chemotherapy in treatment of breast cancer, ovarian cancer, non-small cell lung cancer, and soft tissue sarcoma (orphan). Catharanthus alkaloids have also been used for therapy of acute lymphocytic leukaemia, malignant lymphomas such as Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura and solid tumours, such as metastatic testicular cancer, Ewing’s sarcoma, foetal rhabdomyosarcoma, primary neuroectodermal tumours Wilms’ tumour, and retinoblastoma [23].
Overview on mechanisms of phytochemicals for prevention and treatment of cancer
Cancer has been known as one of several-mechanism carcinogenesis process, which includes several steps such as mutagenic, cell death and epigenetic by associated stages: initiation, promotion, and progression [55, 56]. Cells in humans and other organisms are broadly found in a range of oxidizing agents that are essential for life in several cases [57, 58]. Carcinogenic substance, such as environmental pollutants, dietary mutagens and radiation, will cause to produce ROS and/or reactive nitrogen species (RNS), that react with cellular molecules such as proteins, lipids, and DNA for promotion of carcinogenesis. Regular consumption of phytochemicals directly alleviate ROS/RNS levels and removes carcinogenic reactive intermediates through dietary phytochemicals intake not only scavenge ROS/RNS directly but also eliminate carcinogenic reactive intermediates indirectly transcription factor Nrf2 [nuclear factor erythroid2 p45 (NF-E2)-related factor 2] by involving with antioxidant system. It has been accepted that if Nrf2 is to be released from Kelch-like ECH related with protein 1 (Keap1) and transferred intonucleus, Nrf2 is associated with antioxidant responsive elements (AREs) in the promoter/enhancer site of step II detoxification and antioxidant enzyme genes with the Maf protein. On the other hand, reactivation of Nrf2 could be corrected through supplementation of phytochemicals by epigenetic modifications including DNA methylation and histone correction.
Although, cancer is very complex and certainly cannot treat by nutrient interventions but the use of safe compounds such as phytochemicals can help to some extent in the treatment and prevention of cancer. Regular consumption of phytochemicals can prevent and decrease costs. We recommend to daily use of phytochemicals for prevention of cancer for therapeutic and treatment.
Ethical Considerations

Compliance with ethical guidelines
There was no ethical considerations to be noted in this article.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions
All authors contributed toward data analysis, drafting and revising the paper and agreed to be responsible for all the aspects of this work.
Conflict of interest
The authors declared no conflict of interest.

[1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2): 69–90. [crossref]

[2] Aghajanpour M, Nazer MR, Obeidavi Z, Akbari M, Ezati P, MoradiKor N.  Functional foods and their role in cancer prevention and health promotion: a comprehensive review. Am J Cancer Res. 2017; 7(4): 740-769. [crossref]

[3] Zhang J. Can We Discover “Really Safe and Effective” Anticancer Drugs. Adv Pharmacoepidemiol Drug Safety. 2012; 01(05). [crossref]

[4] Schottenfeld D, Beebe-Dimmer JL, Buffler PA, Omenn GS. Current perspective on the global and United States cancer burden attributable to lifestyle and environmental risk factors. Annu Rev Public Health. 2013; 34: 97–117. [crossref]

[5] Organization, WHO. Cancer: Fact sheet N297, February 2015. [WHO]

[6] Cancer I AF R O. World cancer report 2014. Geneva: WHO (2014).

[7] Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM. The global burden of cancer: priorities for prevention. Carcinogen. 2010; 31: 100–110. [crossref]

[8] Safarzadeh E, SandoghchianShotorbani S, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Advpharmaceutic bull. 2014; 4: 421–427. [crossref]

[9] Qi F, Li A, Inagaki Y, Gao J, Li J, Kokudo N, Li XK, Tang W. Chinese herbal medicines as adjuvant treatment during chemo-or radio-therapy for cancer. Biosci Trends. 2010;4: 297-307. [PMID]
[10] Pereira DM, Valentao P, Correia-da-Silva G, Teixeira N, Andrade PB. Plant secondary metabolites in cancer chemotherapy: where are we? Curr Pharmaceutic Biotechnol. 2012; 13: 632–650. [crossref]

[11] A. Ajith T, Janardhanan K. Indian medicinal mushrooms as a source of antioxidant and antitumor agents. J Clin Biochem Nutr. 2007; 40(3): 157–62. [crossref]

[12] Sun J, Hai Liu R. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. Cancer Lett. 2006; 241(1): 124 34. [crossref]

[13] Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy. J Natl Cancer Inst. 2008; 100(11): 773–83. [crossref]

[14] Lai PK, Roy J. Antimicrobial and chemo preventive properties of herbs and spices. Curr Med Chem. 2004; 11(11): 1451–60. [crossref]

[15] Temple NJ, Wilson T, Jacobs Jr DR. Nutritional health: strategies for disease prevention. Springer Science & Business Media. 2012.

[16] Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003; 78(3 Suppl): 517S–20S. [crossref]

[17] Wang L, Weller CL. Recent advances in extraction of nutraceuticals from plants. Trends Food Sci Technol. 2006; 17(6): 300–12.

[18] Pezzuto JM. Plant-derived anticancer agents. Biochem Pharmacol. 1997; 53(2): 121–33.

[19] Shukla Y, Singh M. Cancer preventive properties of ginger: a brief review. Food Chem Toxicol. 2007; 45(5): 683–90. [crossref]

[20] Aggarwal BB, Kunnumakkara AB, Harikumar KB, Tharakan ST, Sung B, Anand P. Potential of spice-derived phytochemicals for cancer prevention. Planta Med. 2008; 74(13): 1560–9.

[21] Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003; 3(10): 768–80. [crossref]

[22] Mans DR, da Rocha AB, Schwartsmann G. Anti-cancer drug discovery and development in Brazil: targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds. Oncologist. 2000; 5(3):185–98. [crossref]

[23] Lichota A,  Gwozdzinski k. Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci. 2018; 19: 3533.

[24] Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action.  J Nutr. 2004; 134(12 Suppl): 3479S–85S. [crossref]

[25] Block G, Norkus E, Hudes M, Mandel S, Helzlsouer K. Which plasma antioxidants are most related to fruit and vegetable consumption?. Am J Epidemiol. 2001; 154(12): 1113–8. [crossref]

[26] Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr. 2013; 4(3): 384S–92S. [crossref]

[27] Lampe JW, Chang J-L. Interindividual differences in phytochemical metabolism and disposition. Seminar Cancer Biol.  2007; 17: 347-353. [crossref]

[28] Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GL. The flavonoidquercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol. 2012; 83(1): 6–15.

[29] Tamimi RM, Hankinson SE, Campos H, Spiegelman D, Zhang S,Colditz GA, et al. Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol. 2005; 161(2): 153–60. [crossref]

[30] Shen T, Khor SC, Zhou F, Duan T, Xu YY, Zheng YF, etal. Chemoprevention by lipid-soluble tea polyphenols indiethylnitrosamine/phenobarbital –induced hepatic pre-cancerous lesions. Anticancer Res. 2014; 34(2): 683–93. [PMID]
[31] Crozier A, Clifford MN, Ashihara H. Plant secondary metabolites: occurrence, structure and role in the human diet. John Wiley & Sons. 2008. [crossref]

[32] W.Watson G , M. Beaver L , E. Williams D , H. Dashwood R , Ho E. Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention. AAPS J. 2013; 15(4): 951–61. [crossref]

[33] Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr. 2000; 130(8S Suppl): 2073S–85S. [crossref]

[34] Islam MB, Sarkar MMH, Shafique MZ, Jalil MA, Haque MZ, Amin R. Phytochemical screening and anti-microbial activity studies on leeamacrophylla seed extracts. J Sci Res. 2013; 5(2). [crossref]

[35] Chirumbolo S. Plant phytochemicals as new potential drugs for immune disorders and cancer therapy: really a promising path. J Sci Food Agric. 2012; 92(8): 1573–7. [crossref]

[36] Mateos R, Goya L, Bravo L. Uptake and metabolism of hydroxylcinnamic acids (chlorogenic, caffeic, and ferulic acids) by HepG2 cells as a model of the human liver. J Agric Food Chem. 2006; 54(23): 8724–32.

[37] Gulcin I. Antioxidant activity of food constituents: an overview. Arch Toxicol. 2012; 86(3): 345–91. [crossref]

[38] Forster GM, Raina K, Kumar A, Kumar S, Agarwal R, Chen MH, et al. Rice varietal differences in bioactive bran components for inhibition of colorectal cancer cell growth. Food Chem. 2013; 141(2): 1545–52. [crossref]

[39] Murakami A. Modulation of protein quality control systems by food phytochemicals. J Clin Biochem Nutr. 2013; 52(3): 215–27.

[40] Kelly EH, Anthony RT, Dennis JB. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002; 13: 572–584. [crossref]

[41] Kumar S, Mishra A, Pandey AK. Antioxidant mediated protective effect of Parthenium hysterophorus against oxidative damage using in vitro models. BMC Complement Altern Med. 2013; 13: 120-130. [crossref]

[42] Kumar S,Pandey AK. Phenolic content, reducing power and membrane protective activities of Solanum xanthocarpum root extracts. Vegeto .  2013; 26: 301–307. [PMID]

[43] Duthie GG, Duthie SJ, Kyle JAM. Plant polyphenolsin cancer and heart disease: implications as nutritional antioxidants. Nutr Res Rev. 2000; 13: 79–106. [crossref]

[44] Giardi MT, Touloupakis E, Bertolotto D, Mascetti G. Preventive or potential therapeutic value of nutraceuticals against ionizing radiation-induced oxidative stress in exposed subjects and frequent fliers. Int J Mol Sci. 2013; 14(8): 17168–92. [crossref]

[45] Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr. 2013; 4(3): 384S–92S. [crossref]

[46] Rajkapoor B, Murugesh N, Chodon D, Sakthisekaran D. Chemoprevention of N-nitrosodiethylamine induced phenobarbitol promoted liver tumors in rat by extract of Indigoferaaspalathoides. Biol Pharm Bull. 2005; 28(2): 364–6. [crossref]

[47] MollakhaliliMeybodi N,Mortazavian AM, BahadoriMonfared A,Sohrabvandi S, AghaeiMeybodi F. Phytochemicals in cancer prevention: A review of the evidence. Iran J Cancer Prev. 10(1): e7219. [crossref]

[48] Russo GL. Ins and outs of dietary phytochemicals in cancer chemoprevention. Biochem Pharmacol. 2007; 74(4): 533–44.

[49] Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007; 39(1): 44–84. [crossref]

[50] Deiters A, Martin SF. Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis. Chem Rev. 2004; 104(5): 2199–238. [crossref]

[51] Su C, Zhang P, Song X, Shi Q, Fu J, Xia X, et al. Tetrachlorobenzoquinone activates Nrf2 signaling by Keap1 cross-linking and ubiquitin translocation but not Keap1-Cullin3 complex dissociation. Chem Res Toxicol. 2015; 28(4): 765–74. [crossref]

[52] Chikamori K, Grozav AG, Kozuki T, Grabowski D, Ganapathi R, GanapathiMK. DNA topoisomerase II enzymes as molecular targets for cancer chemotherapy. Curr Cancer Drug Targets. 2010; 10(7): 758–71. [PMID]

[53] Bhandari PR. Crocus sativus L. (saffron) for cancer chemoprevention: A mini review. J Tradit Complement Med. 2015; 5(2): 81–7.

[54] Ouyang L, Luo Y, Tian M, Zhang SY, Lu R, Wang JH, et al. Plant natural products: from traditional compounds to new emerging drugsin cancer therapy. Cell Prolif. 2014; 47(6): 506–15.

[55] Hemler ME. Tetraspanin proteins promote multiple cancer stages. Nat Rev Cancer. 2014; 14(1): 49–60. [PMID]

[56] Sun B, Karin M. The therapeutic value of targeting inflammation in gastrointestinal cancers. Trends Pharmacol Sci. 2014; 35(7): 349–57. [crossref]

[57] Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem. 2002; 50(25): 7449–54.

[58] Arumugam A, Stout M, Tsin C, Bhat A, Yong T, Nandy S, et al. Abstract 199: Short-term treatment with pregnancy levels of estradiol prevents breast cancer by delaying promotion and progression. Cancer Res. 2014; 73(8 Supplement): 199. [crossref]
Type of Study: Review Article | Subject: Cancer Biology
Received: 2018/08/5 | Accepted: 2018/09/27 | Published: 2018/10/15

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