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Moringa oleifera Lam: Targeting Chemoprevention

  • Published : 2016.08.01

Abstract

Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as ''murungai'' or ''kelor''. Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research need to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

Keywords

References

  1. Abdull Razis AF, Ibrahim MD, Kntayya SB, et al (2014). Health benefit of Moringa oleifera. Asian Pac J Cancer Prev, 20, 8571-6.
  2. Adam HM, Nur KAD, Dyaningtyas P, et al (2012). Ethanolic extract of Moringa oleifera increased cytotoxic effect of doxorubicin on HeLa cancer cells. J Nat Remedies, 12, 108-4.
  3. Amaglo NK, Bennett RN, Lo C, et al (2010). Profiling selected phytochemicals and nutrients in different tissues of the multipurpose tree Moringa oleifera L., grown in Ghana. Food Chem, 122, 1047-54. https://doi.org/10.1016/j.foodchem.2010.03.073
  4. Anand P, Ajaikumar B, Kunnumakara CS, et al (2008). Cancer is a Preventable Disease that Requires Major Lifestyle Changes. Pharm Res, 25, 2097-16. https://doi.org/10.1007/s11095-008-9661-9
  5. Anwar F, Bhanger MI (2003). Analytical characterization of Moringa oleifera seed oil grown in temperate regions of Pakistan. J Agric Food Chem, 51, 6558-63. https://doi.org/10.1021/jf0209894
  6. Anwar F, Ashraf M, Bhanger MI (2005). Interprovenance variation in the composition of Moringa oleifera oilseeds from Pakistan. J Am Oil Chem Soc, 82, 45-51. https://doi.org/10.1007/s11746-005-1041-1
  7. Anwar F, Latif S, Ashraf M, et al (2007). Moringa oleifera: A Food Plant with Multiple Medicinal Uses. Phytother Res, 25, 17-5.
  8. Ali EN, Musa N (2013). An investigation of anticancer effect of Moringa oleifera. ISSB 2013.
  9. Asare GA, Gyan B, Bugyei K, et al (2012). Toxicity potentials of the nutraceutical Moringa oleifera at supra-supplementation levels. J Ethnopharmacol, 139, 265-72. https://doi.org/10.1016/j.jep.2011.11.009
  10. Ashkenazi Avi (2008). Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor rev, 3, 325-31.
  11. Baba AI, Catoi C (2007) Comparative oncology. bucharest: the publishing house of the romanian academy.
  12. Barillari J, Gueyrard D, Rollin P, et al (2001). Barbarea verna as a source of 2-phenylethyl glucosinolate precursor of cancer chemopreventive phenylethyl isothiocyanate. Fitoterapia, 72, 760-764. https://doi.org/10.1016/S0367-326X(01)00320-3
  13. Bharali R, Tabassum J, Azad MRH (2003). Chemomodulatory effect of Moringa oleifera Lam, on hepatic carcinogen metabolising enzymes, antioxidant parameters and skin papillomagenesis in mice. Asian Pacific J Cancer Prev, 4, 131-9.
  14. Boghossian S, Hawash A (2012). Chemoprevention in colorectal cancer-where we stand and what we have learned from twenty year's experience. Surgeon, 10, 43-52. https://doi.org/10.1016/j.surge.2011.07.003
  15. Brunelli DA, Tavecchio M, Falcioni C, et al (2010). The isothiocyanate produced from glucomoringin inhibits NF-${\kappa}B$ and reduces myeloma growth in nude mice in vivo. Biochem Pharmacol, 79, 1141-8. https://doi.org/10.1016/j.bcp.2009.12.008
  16. Budda S, Butryee C, Tuntipopipat S, et al (2011). Suppressive effects of Moringa oleifera lam pod against mouse colon carcinogenesis induced by azoxymethane and dextran sodium sulfate. Asian Pac J Cancer Prev, 12, 3221-8.
  17. Butryee C (2010). Nutritive evaluation and effect of moringa oleifera pod on clastogenic potential in the mouse. Asian Pac J Cancer Prev, 11, 627-32.
  18. Chadamas P, Piengchai K, Siriporn T, et al (2010). Nutritive evaluation and effect of Moringa oleifera pod on clastogenic potential in the mouse. Asian Pac J Cancer Prev, 11, 627-32.
  19. Charlette T, Alisa P, Anil AC (2013). The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells. Bmc Complem Altern M, 13, 226. https://doi.org/10.1186/1472-6882-13-226
  20. Circu ML, Aw TY (2010). Reactive oxygen species, cellular redox systems, and apoptosis. Free Rad Biol Med, 48, 749-62. https://doi.org/10.1016/j.freeradbiomed.2009.12.022
  21. Chumark P, Khunawat P, Sanvarinda Y, et al (2008). The in vitro and ex vivo antioxidant properties, hypolipidaemic and antiatherosclerotic activities of water extract of Moringa oleifera Lam. leaves. J Ethnopharmacol, 3, 439-46.
  22. Cory S, Adams JM (2002). The Bcl-2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer, 2, 647-56. https://doi.org/10.1038/nrc883
  23. Denault JB, Salvesen GS (2003). Human caspase-7 activity and regulation by its N-terminal peptide. J Biol Chem, 278, 34042-50. https://doi.org/10.1074/jbc.M305110200
  24. Dinkova-Kostova AT, Holtzclaw WD, Cole RN, et al (2002). Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci U.S.A, 18, 11908-13.
  25. Ding X, Wang MY, Yao YX, et al (2010). Protective effect of 5-hydroxymethylfurfural derived from processed Fructus corni on human hepatocyte L02 injured by hydrogen peroxide and its mechanism. J Ethnopharmacol, 128, 373-6. https://doi.org/10.1016/j.jep.2010.01.043
  26. Donepudi M, Mac Sweeney A, Briand C, et al (2003). Insights into the regulatory mechanism for caspase-8 activation. Mol Cell, 11, 543-9. https://doi.org/10.1016/S1097-2765(03)00059-5
  27. D’Souza J, Kulkarni AR (1993). Comparative studies on nutritive values of tender foliage of seedlings and mature plants of Moringa oleifera Lam. J Econ Taxonomic Bot, 17, 479-85.
  28. Durling LJK, Busk L, Hellman BE (2006). Evaluation of the DNA damaging effect of the heat-induced food toxicant 5-hydroxymethylfurfural (HMF) in various cell lines with different activities of sulfotransferases. Food Chem Toxicol, 47, 880-4.
  29. Eilert UB, Wolters A, Nahrstedt, et al (1981).The antibiotic principle of seeds of Moringa oleifera and Moringa stenopetala. Planta Med, 42, 55-61 https://doi.org/10.1055/s-2007-971546
  30. Faizi S, Siddiqui B, Saleem R, et al (1994). Isolation and structure elucidation of new nitrile and mustard oil glycosides from Moringa oleifera and their effect on blood pressure. J Nat Prod, 57, 1256-61. https://doi.org/10.1021/np50111a011
  31. Fan CD, Jiang J, Yin X, et al (2012). Purification of seleniumcontaining allophycocyanin from selenium-enriched Spirulina platensis and its hepatoprotective effect against t-BOOH-induced apoptosis. Food Chem, 34, 253-61.
  32. Fischer U, Janicke RU, Schulze-Osthoff K (2003). Many cuts to ruin: a comprehensive update of caspase substrates. Cell Death Differ, 10, 76-100. https://doi.org/10.1038/sj.cdd.4401160
  33. Flora SJS, Pachauri V (2011). Nuts and Seeds in Health and Disease Prevention. Divis Pharmacol Toxic, 775-85.
  34. Forster N, Ulrichs C, Schreiner M, et al (2015) Development of a reliable extraction and quantification method for glucosinolates in Moringa oleifera. Food Chem, 166, 456- 64. https://doi.org/10.1016/j.foodchem.2014.06.043
  35. Foti Cuzzola V, Galuppo M, Iori R, et al (2013). Beneficial effects of (RS)-glucoraphanin on the tight junction dysfunction in a mouse model of restraint stress. Life Sci, 93, 288-305 https://doi.org/10.1016/j.lfs.2013.07.003
  36. Fulda S, Debatin KM (2006). Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 34, 4798- 881.
  37. Fuglie LJ (1999). The miracle tree: moringa oleifera. natural nutrition for the tropics. church world service, dakar. revised in 2001 and published as the miracle Tree. Multiple Attributes Moringa, 68, 172.
  38. Galuppo M, Nicola GRD, Iori R, et al (2013). Antibacterial activity of glucomoringin bioactivated with myrosinase against two important pathogens affecting the health of long-term patients in hospitals. Molecules, 18, 14340-8. https://doi.org/10.3390/molecules181114340
  39. Galuppo M, Nicola GRD, Iori R, et al (2014). Antiinflammatory activity of glucomoringin isothiocyanate in a mouse model of experimental autoimmune encephalomyelitis. Fitoterapia, 95, 160-74. https://doi.org/10.1016/j.fitote.2014.03.018
  40. Ganesan SK, Singh R, Roy Choudhury D, et al (2014). Genetic diversity and population structure study of drumstick (Moringa oleifera Lam.) using morphological and SSR markers. Ind Crops Prod, 60, 316-25. https://doi.org/10.1016/j.indcrop.2014.06.033
  41. Ghazali HM, Mohammed AS (2011). Nuts and seeds in health and disease prevention. Nuts Seeds Heal Dis Prev, Elsevier.
  42. Ghosh N (2013). Anticancer effect of moringa oleifera leaf extract on human breast cancer cell, 1-57.
  43. Guevara AP, Vargas C, Sakurai H, et al (1999). An antitumor promoter from Moringa oleifera Lam. Mutat Res Toxicol Environ Mutagen, 2,181-8.
  44. Gueyrard D, Barillari J, Iori R, et al (2000). First synthesis of an O-glycosylated glucosinolate isolated from Moringa oleifera, 41, 8307-9. https://doi.org/10.1016/S0040-4039(00)01466-0
  45. Gupta SC, Kim JH, Prasad S, et al (2010). Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev, 29, 405-34 https://doi.org/10.1007/s10555-010-9235-2
  46. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: The next generation. Cell, 5, 646-74.
  47. Hongmei Z (2012). Extrinsic and intrinsic apoptosis signal pathway review scientist. Intech, 3-22.
  48. Itoh K, Wakabayashi N, Katoh Y, et al (1999). Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev, 1, 76-86.
  49. Jaiswal D, Kumar RP, Kumar A, et al (2009). Effect of Moringa oleifera Lam. leaves aqueous extract therapy on hyperglycemic rats. J Ethnopharmacol, 123, 392-6. https://doi.org/10.1016/j.jep.2009.03.036
  50. Jaiswal D, Rai PK, Mehta S, et al (2013). Role of moringa oleifera in regulation of diabetes-induced oxidative stress. Asian Pac J Trop Med, 6, 426-32. https://doi.org/10.1016/S1995-7645(13)60068-1
  51. Jeong WS, Kim JW, Hu R, et al (2004). Modulatory properties of various natural chemopreventive agents in the activation of NF-${\kappa}B$ signalling pathway. Pharm Res, 21, 661-70. https://doi.org/10.1023/B:PHAM.0000022413.43212.cf
  52. Kang W, Lee D, Park CR (2012). Nest distribution of magpies Pica pica sericea as related to habitat connectivity in an urban environment. Landsc Urban Plan, 104, 212-19. https://doi.org/10.1016/j.landurbplan.2011.10.014
  53. Kasolo JN, Bimenya GS, Ojok L, et al (2010). Phytochemicals and uses of Moringa oleifera leaves in Ugandan rural communities. J Med Plants Res, 4, 753-7.
  54. Katayon S, Noor MJMM, Asma M, et al (2006). Effects of storage conditions of Moringa oleifera seeds on its performance in coagulation. Bioresour Technol, 13, 1455-60.
  55. Kaur J, Vaish V, Sanyal, et al (2012). COX-2 as a molecular target of colon cancer chemoprevention: Promise and reality. Biomed Aging Pat, 3, 67-72.
  56. Khatik GL, Kaur J, Kumar V, et al (2012). 1,2,4-Oxadiazoles: A new class of anti-prostate cancer agents. Med Chem Lett, 22, 1912-16. https://doi.org/10.1016/j.bmcl.2012.01.059
  57. Kjaer AO, Malver B, El-Menshawi, et al (1979). Isothiocyanates in myrosinase-treated seed extracts of Moringa peregrina. Phytochem, 18, 1485-7 https://doi.org/10.1016/S0031-9422(00)98480-2
  58. Kobayashi A, Kang MI, Watai Y, et al (2006). Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Molecules Cell Biol, 1, 221-9.
  59. Kou X, Kirberger M, Yang Y, et al (2013). Natural products for cancer prevention associated with Nrf2-ARE pathway. Food Sci Hum Wellness, 2, 22-28. https://doi.org/10.1016/j.fshw.2013.01.001
  60. Kundu J, Chun K, Aruoma OI, et al (2014). Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of thymoquinone. Fundam Mol Mech Mutagen, 768, 22-34. https://doi.org/10.1016/j.mrfmmm.2014.05.003
  61. Lambole V, Kumar U (2012). Effect of moringa oleifera lam. on normal and dexamethasone suppressed wound healing. Asian Pac J Trop Biomed, 2, 219-23. https://doi.org/10.1016/S2221-1691(12)60163-4
  62. Lee H, Oh ET, Choi BH, et al (2015). NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation. Sci Rep, 5, 7769. https://doi.org/10.1038/srep07769
  63. Leonarduzzi C, Leonardi S, Menozzi P, et al (2012).Towards an optimal sampling effort for paternity analysis in forest trees: what do the raw numbers tell us? iForest - Biogeosciences For, 1, 18-25.
  64. Lettre DP, Mishra G, Singh P, et al (2011). Traditional uses, phytochemistry and pharmacological properties of moringa oleifera plant: An overview. Der Pharmacia Lettre, 2, 141-64.
  65. Levine A, Belenghi B, Damari-Weisler H, et al (2001). Vesicleassociated membrane protein of Arabidopsis suppresses Bax induced apoptosis in yeast downstream of oxidative burst. J Biol Chem, 276, 46284-9. https://doi.org/10.1074/jbc.M107375200
  66. Li-Weber M (2010). Targeting apoptosis pathways in cancer by Chinese medicine. Cancer Lett, 2, 304-12.
  67. Lockshin RA, Zakeri Z (2007).Cell death in health and disease. J Cell Mol Med, 11, 1214-24. https://doi.org/10.1111/j.1582-4934.2007.00150.x
  68. Luo H, Rankin GO, Li Z, et al (2011). Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway. Food Chem, 2, 513-9.
  69. Machuy N, Raja lingam K, Rudel T (2004). Requirement of caspase mediated cleavage of c-Abl during stress-induced apoptosis. Cell Death Differ, 11, 90-300. https://doi.org/10.1038/sj.cdd.4401307
  70. Ma C, Song M, Zhang Y, et al (2014). Nickel nanowires induce cell cycle arrest and apoptosis by generation of reactive oxygen species in HeLa cells. Toxicol Reports,1, 114-21. https://doi.org/10.1016/j.toxrep.2014.04.008
  71. Mahajan SG, Mehta Aa (2010). Immunosuppressive activity of ethanolic extract of seeds of Moringa oleifera Lam. in experimental immune inflammation. J Ethnopharmacol, 130, 183-6. https://doi.org/10.1016/j.jep.2010.04.024
  72. Mahmood Z, Shukla Y (2010). Death receptors: targets for cancer therapy. Exp Cell Res, 316, 887-99. https://doi.org/10.1016/j.yexcr.2009.12.011
  73. Mehta LK, Balaraman R, Amin AH, et al (2003). Effect of fruits of moringa oleifera on the lipid profile of normal and hypercholesterolaemic rabbits. J Ethnopharmacol, 86, 191-5. https://doi.org/10.1016/S0378-8741(03)00075-8
  74. Morse DE, Pendrys DG, Katz RV, et al (2000). Food group intake and the risk of oral epithelial dysplasia in a United States population. Cancer Cause Contr, 11, 713-20. https://doi.org/10.1023/A:1008943904085
  75. Moyo B, Oyedemi S, Masika PJ, et al (2012). Polyphenolic content and antioxidant properties of Moringa oleifera leaf extracts and enzymatic activity of liver from goats supplemented with Moringa oleifera leaves/sunflower seed cake. Meat Sci. 91, 441-7. https://doi.org/10.1016/j.meatsci.2012.02.029
  76. Mueller M, Hobiger S, Jungbauer A (2010). Anti-inflammatory activity of extracts from fruits, herbs and spices. Food Chem. 122, 987-96. https://doi.org/10.1016/j.foodchem.2010.03.041
  77. Mukhtar H (2012). Chemoprevention: making it a success story for controlling human cancer. Cancer Lett. 326, 123-7. https://doi.org/10.1016/j.canlet.2012.05.016
  78. Nada Y, Kalaany, Sabatini DM (2008). NIH Public Access, 2, 157-62.
  79. Nadkarni KM (2009). Indian materia indica. Bombay popular prakashan, 1, 811-6.
  80. Nakao S, Mabuchi M, Shimizu T, et al (2014). Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorganic Med Chem Lett. 24, 1071-1074. https://doi.org/10.1016/j.bmcl.2014.01.008
  81. Nathan SS,Venkataswera R, Gopalakrishnan V, et al (1999 ). Anti- inflammatory activity of Moringa oliefera. Lam Anc Sc Life, 18, 198-200.
  82. Neergheen VS, Bahorun T, Will E, et al (2010). Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention. Toxicol, 278, 229-41. https://doi.org/10.1016/j.tox.2009.10.010
  83. Nikolova M, Berkov S, Ivancheva S (2004). A rapid TLC method for analysis of external flavonoids aglycones in plant exudates. ACTA Chromol, 14, 10-114.
  84. Oueslati S, Ksouri R, Falleh H, et al (2012). Phenolic content, antioxidant, anti-inflammatory and anticancer activities of the edible halophyte Suaeda fruticosa Forssk. Food Chem 2, 943-7.
  85. Patel P, Patel N, Patel D, et al (2014).Phytochemical Analysis and Antifungal Activity of Moringa Oleifera. Int J Pharm Sci, 6, 144-7.
  86. Popoola JO, Obembe OO (2013). Local knowledge, use pattern and geographical distribution of Moringa oleifera Lam. (Moringaceae) in Nigeria. J Ethnopharmacol, 150, 682-91. https://doi.org/10.1016/j.jep.2013.09.043
  87. Rashid U, Anwar F, Moser BR, et al (2008). Moringa oleifera oil: a possible source of biodiesel. Bioresour Technol, 99, 8175-9. https://doi.org/10.1016/j.biortech.2008.03.066
  88. Ratshilivha N, Awouafack MD, du Toit ES, et al (2014). The variation in antimicrobial and antioxidant activities of acetone leaf extracts of 12 Moringa oleifera (Moringaceae) trees enables the selection of trees with additional uses. South African J Bot, 92, 59-64. https://doi.org/10.1016/j.sajb.2014.02.002
  89. Ray K, Hazrai R, Guha D (2003). Central inhibitory effect of Moringa oleifera root extract: possible role of neurotransmitters. Indian J Exp Biol, 41, 1279–84.
  90. Ray K, Hazra R, Debnath PK, et al (2004). Role of 5-hydroxytryptamine in Moringa oleifera induced potentiation of pentobarbitone hypnosis in albino rats. Indian J Exp Biol, 42, 632-5.
  91. Repnik U, Stoka V, Turk V, et al (2012). Lysosomes and lysosomal cathepsins in cell death. Biochim Biophys Acta, 10, 22-33.
  92. Rollin P, Tatibouet A (2011). Glucosinolates: The synthetic approach. Comptes Rendus Chim, 14, 194-210. https://doi.org/10.1016/j.crci.2010.05.002
  93. Rupjyoti B, Jawahira T, Mohammed RHA (2003). Chemomodulatory effect of Moringa oleifera on hepatic carcinogen metabolizing enzymes, antioxidant parameters and skin papillomagenesis in mice. Asian Pac J Prev, 4, 131-9.
  94. Saha D (2013). Moringa species ( Moringaceae ): phytochemistry, cancer chemoprevention potentials with advanced traditional medicinal practice. J Natural App Sc (Tanzania), 1, 634-6.
  95. Santos AFS, Argolo ACC, Coelho LCBB, et al (2005). Detection of water soluble lectin and antioxidant component from Moringa oleifera seeds. Water Res, 39, 975-80. https://doi.org/10.1016/j.watres.2004.12.016
  96. Sarker KP, Obara S, Nakata M, et al (2000). Anandamide induces apoptosis of PC-12 cells: involvement of superoxide and caspase-3. FEBS Letter, 472, 39-44. https://doi.org/10.1016/S0014-5793(00)01425-3
  97. Saravanan BC, Sreekumar C, Bansal GC, et al (2003). Arapid MTT colorimetric assay to assess the proliferation index of two Indian strains of Theileria annulata. Veterinary Parasit, 113, 211-6. https://doi.org/10.1016/S0304-4017(03)00062-1
  98. Sauberlich HE (1984). Implications of nutritional status on human biochemistry, physiology, and health. Clin Biochem, 17, 132-142. https://doi.org/10.1016/S0009-9120(84)90344-8
  99. Schliephacke T, Meinl A, Kratzmeier M, et al (2004). The telomeric region is excluded from nucleosomal fragmentation during apoptosis, but the bulk nuclear chromatin is randomly degraded. Cell Death Differ, 11, 693-700. https://doi.org/10.1038/sj.cdd.4401414
  100. Severin I, Dumont C, Jondeau-Cabaton A, et al (2010). Genotoxic activities of the food contaminant 5-hydroxymethylfurfural using different in vitro bioassays. Toxicol Letters, 192, 189-94. https://doi.org/10.1016/j.toxlet.2009.10.022
  101. Shah V, Shah S, Shah H, et al (2012). Antibacterial activity of polymer coated cerium oxide nanoparticles. PLoS One, 7, 47827. https://doi.org/10.1371/journal.pone.0047827
  102. Sharma V, Paliwal R, Janmeda P, et al (2012). Renoprotective effects of Moringa oleifera pods in 7, 12 dimethylbenz[a] Medicinal plants from Riau province, Sumatra, Indonesia. J Chin Int Med, 10, 1171-8.
  103. Sharma V, Paliwal R, Janmeda P, et al (2012). Chemopreventive Efficacy of Moringa oleifera Pods Against 7, 12-Dimethylbenz[a]anthracene Induced Hepatic Carcinogenesis in Mice. Asian Pac J Cancer Prev, 13, 2563-69. https://doi.org/10.7314/APJCP.2012.13.6.2563
  104. Sharma V, Paliwal R (2012). Chemoprotective role of Moringa oleifera and its isolated saponin against DMBA induced tissue damage in male mice: A histopathological analysis. Int J Drug Dev Res, 4, 215-28
  105. Shruti N, Varalakshmi KN (2011). Anticancer, cytotoxic potential of Moringa oleifera extracts on HeLa cell line, J Nat Pharm, 3, 234-7.
  106. Sirintip B, Chaniphun B, Siriporn T, et al (2011). Suppressive effects of Moringa oleifera Lam pod against mouse colon carcinogenesis induced by azoxymethane and dextran sodium sulfate. Asian Pac J Cancer Prev, 12, 3221-28.
  107. Sreelatha SA, Jeyachitra B, Padma PR (2011). Antiproliferation and induction of apoptosis by Moringa oleifera leaf extraction human cancer cells. Food Chem Toxicol, 6, 1270-5.
  108. Srivastava SK, Singh SV (2004). Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells. Carcinogenesis, 9, 701-9.
  109. Srivastava JK, Gupta S (2006). Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells. Biochem Biophys Res Commun, 346, 447-53. https://doi.org/10.1016/j.bbrc.2006.05.147
  110. Soslow R, Dannenberg A, Rush D, et al (2000). Cox-2 is expressed in human pulmonary colonic and mammary tumors. Cancer, 89, 2637-45. https://doi.org/10.1002/1097-0142(20001215)89:12<2637::AID-CNCR17>3.0.CO;2-B
  111. Sporn MB (1976). Approaches to prevention of epithelial cancer during preneoplastic period. Cancer Res, 36, 2699-702.
  112. Suphachai C (2014). Antioxidant and anticancer activities of Moringa oleifera leaves. J Med Plant Res, 7, 318-25.
  113. Tahir K, Tahira M, Haq IU (2010). Moringa oleifera: a natural gift-A review, 2, 775-81.
  114. Tanaka T, (2013). Role of Apoptosis in the Chemoprevention of Cancer. J Exp Clin Med, 5, 89-91. https://doi.org/10.1016/j.jecm.2013.04.001
  115. Thatte U, Bagadey S, Dahanukar S (2000). Modulation of programmed cell death by medicinal plants. Cell Mol Biol, 46, 199-14.
  116. Thompson CB (1995). Apoptosis in the pathogenesis and treatment of disease. Science, 267, 1456-62. https://doi.org/10.1126/science.7878464
  117. Trees for Life (2005). Moringa Book [Brochure]. Wichita, Kansas: Balbir Mathur.
  118. Vasanth K, Ilango K, Mohan K, et al (2014). Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction. Biointerfaces, 117, 354-9. https://doi.org/10.1016/j.colsurfb.2014.02.052
  119. Verma AR, Vijayakumar M, Mathela CS, et al (2009). In vitro and in vivo antioxidant properties of different fractions of Moringa oleifera leaves. Food Chem Toxicol, 47, 2196-201. https://doi.org/10.1016/j.fct.2009.06.005
  120. Veena S, Ritu P, Pracheta J, et al (2012). Chemopreventive efficacy of Moringa oleifera pods against 7, 12-dimethylbenz(a) anthracene induced hepatic carcinogenesis in mice. Asian Pac J Cancer Prev, 13, 2563-9. https://doi.org/10.7314/APJCP.2012.13.6.2563
  121. Wang Y, Liu C, Luo M, et al (2015). Chemotherapy-induced miRNA-29c/catenin-signaling suppresses metastasis in gastric cancer. Cancer Res. 75, 1332-44. https://doi.org/10.1158/0008-5472.CAN-14-0787
  122. Wang SV, Jiao H (2001). Changes in oxygen-scavenging systems and membrane lipid peroxidation during maturation and ripening in black berry. J Agric Food Chem, 49, 1612-9. https://doi.org/10.1021/jf0013757
  123. Waterman C, Cheng DM, Rojas-Silva P, et al (2014). Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro. Phytochem, 103, 114-22. https://doi.org/10.1016/j.phytochem.2014.03.028
  124. Wen S, Niu Y, Lee SK, et al (2014). Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death. Cancer Treat Rev, 1, 31-40.
  125. Wu G (2010). Functional Amino Acids in Growth. Adv Nutr, 1, 31-37. https://doi.org/10.3945/an.110.1008
  126. Wu S, Teik L, Lin C (2005). Effects of antioxidants and caspase-3 inhibitor on the phenylethyl isothiocyanateinduced apoptotic signaling pathways. Europ J Pharmacol, 518, 96-106. https://doi.org/10.1016/j.ejphar.2005.06.021
  127. Wu X, Patterson S, Hawk E (2011). Chemoprevention history and general principles. Best Pract Res Clin Gastroenterol, 25, 445-59. https://doi.org/10.1016/j.bpg.2011.10.012
  128. Yang LL, Lee CY, Yen KY (2000). Induction of apoptosis by hydrolysable tannin from Eugenia jambos L. On human leukemia cells. Cancer Letters, 157, 65-7. https://doi.org/10.1016/S0304-3835(00)00477-8
  129. Zeb A, Sadiq A, Ullah F, et al (2014). Phytochemical and toxicological investigations of crude methanolic extracts , subsequent fractions and crude saponins of Isodon rugosus. Biol Res, 47, 1-6.
  130. Zhang DD, Hannink M (2003). Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol, 22, 8137-51.
  131. Zhang DD, Lo SC, Sun Z, et al (2005).Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. J Biol Chem, 34, 30091-9.
  132. Zhang X, Bommareddy A, Chen W, et al (2009). Sarcophinediol, a Chemopreventive Agent of Skin Cancer, Inhibits Cell Growth and Induces Apoptosis through Extrinsic Pathway in Human Epidermoid Carcinoma A431 Cells. Transl Oncol, 2, 21-30. https://doi.org/10.1593/tlo.08190
  133. Zhang Y, Talalay P (1994). Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Res, 54, 1976-81.
  134. Zhang Y (2004). Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action. Mutation Res, 2, 173-90.
  135. Zhao CR, Gao ZH, Qu XJ (2014). Nrf2-ARE signaling pathway and natural products for cancer chemoprevention. Cancer Epidem, 5, 523-33.