A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

Jung,Il  Lae; Lee,Ju  Hye; Kang,Se  Chan

doi:10.3892/ol.2015.3482

A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

Authors:
- Il Lae Jung
- Ju Hye Lee
- Se Chan Kang
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Affiliations: Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, Republic of Korea, Department of Life Science, Gachon University, Seongnam, Gyeonggi, Republic of Korea
Published online on: July 10, 2015 https://doi.org/10.3892/ol.2015.3482
Pages: 1597-1604

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Abstract

It has previously been reported that cold water-extracts of Moringa oleifera leaf have anticancer activity against various human cancer cell lines, including non‑small cell lung cancer. In the present study, the anticancer activity of M. oleifera leaf extracts was investigated in human hepatocellular carcinoma HepG2 cells. By the analysis of apoptotic signals, including the induction of caspase or poly(ADP‑ribose) polymerase cleavage, and the Annexin V and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assays, it was demonstrated that M. oleifera leaf extracts induce the apoptosis of HepG2 cells. In the hollow fiber assay, oral administration of the leaf extracts significantly reduced (44‑52%) the proliferation of the HepG2 cells and A549 non‑small cell lung cancer cells. These results support the potential of soluble extracts of M. oleifera leaf as orally administered therapeutics for the treatment of human liver and lung cancers.

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1	Khalafalla MM, Abdellatef E, Dafalla HM, et al: Active principle from Moringa oleifera lam leaves effective against two leukemias and a hepatocarcinoma. Afr J Biotechnol. 9:8467–8471. 2010.
2	Iqbal S and Bhanger MI: Effect of season and production location on antioxidant activity of Moringa oleifera leaves grown in Pakistan. J Food Compos Anal. 19:544–555. 2006. View Article : Google Scholar
3	Wood M: The book of herbal wisdom: Using plants as medicine. 1st. North Atlantic Books; Berkeley, CA, USA: pp. 3741997
4	Oliveira JTA, Silveira SB, Vasconcelos KM, Cavada BS and Moreira RA: Compositional and nutritional attributes of seeds from the multiple purpose tree Moringa oleifera Lamarck. J Sci Food Agric. 79:815–820. 1999. View Article : Google Scholar
5	Fahey JW: Moringa oleifera: a review of the medical evidence for its nutritional, therapeutic, and prophylactic properties. Part 1. Trees for Life Journal. 1:52005.
6	Fuglie LJ: The Miracle Tree: Moringa oleifera: Natural Nutrition for the Tropics. Church World Service, Dakar. Revised in 2001 and published as The Miracle Tree: The multiple attributes of Moringa. 68–172. 1999.
7	Mukunzi D, Nsor-Atindana J, Xiaoming Z, Gahungu A, Karangwa E and Mukamurezi G: Comparison of volatile profile of Moringa oleifera leaves from Rwanda and China using HS-SPME. Pak J Nutrit. 10:602–608. 2011. View Article : Google Scholar
8	Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K and Gilani AH: Fully acetylated carbamate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry. 38:957–963. 1995. View Article : Google Scholar : PubMed/NCBI
9	Kooltheat N, Sranujit RP, Chumark P, Potup P, Laytragoon-Lewin N and Usuwanthim K: An ethyl acetate fraction of Moringa oleifera Lam. Inhibits human macrophage cytokine production induced by cigarette smoke. Nutrients. 6:697–710. 2014. View Article : Google Scholar : PubMed/NCBI
10	Mahmood KT, Mugal T and Haq IU: Moringa oleifera: A natural gift-A review. J Pharm Sci Res. 2:775–781. 2010.
11	Anwar F, Latif S, Ashraf M and Gilani AH: Moringa oleifera: a food plant with multiple medicinal uses. Phytother Res. 21:17–25. 2007. View Article : Google Scholar : PubMed/NCBI
12	Olusola ATE: The miracle tree: Moringa oleifera (drumstick)Archive Vibrant Health with Nature. (Keep Hope Alive Series). Unijos Consultancy Limited Press; Jos, Nigeria: pp. 120–136. 2006
13	Ijarotimi OS, Adeoti OA and Ariyo O: Comparative study on nutrient composition, phytochemical, and functional characteristics of raw, germinated, and fermented Moringa oleifera seed flour. Food Sci Nutr. 1:452–463. 2013. View Article : Google Scholar : PubMed/NCBI
14	Moyo B, Oyedemi S, Masika PJ and Muchenje V: 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. 91:441–447. 2012. View Article : Google Scholar : PubMed/NCBI
15	Busani M, Masika PJ, Hugo A, et al: Nutritional characterization of Moringa (Moringa oleifera Lam.) leaves. Afr J Biotechnol. 10:12925–12933. 2011.
16	Waldron KW, Parker ML and Smith AC: Plant cell wall and food quality. J Sci Food Technol. 2:109–110. 2003.
17	Tetteh ONA: Effects of blanching and dehydration methods on the quality of Moringa leaf powder used as herbal green tea (unpublished Master's thesis)Kwame Nkrumah University; Ghana: 2008
18	Fuglie LJ: Combating malnutrition with MoringaThe Miracle Tree: The Multiple Attributes of Moringa. Fuglie LJ: CTA Publication; Wageningen, The Netherlands: pp. 117–136. 2001
19	Ayotunde EO, Fagbenro OA and Adebanyo OT: Toxicity of aqueous extract of Moringa oleifera seed powder to Nile tilapia (Oreochromis niloticus) fingerlings. Int Res J Agric Sci. 1:142–150. 2011.
20	Chumark P, Khunawat P, Sanvarinda Y, et al: The in vitro and ex vivo antioxidant properties, hypolipidaemic and antiatherosclerotic activities of water extract of Moringa oleifera Lam leaves. J Ethnopharmacol. 116:439–446. 2008. View Article : Google Scholar : PubMed/NCBI
21	Miyoshi N, Takabayashi S, Osawa T and Nakamura Y: Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: implication for prevention against inflammation-related carcinogenesis. Carcinogenesis. 25:567–575. 2004. View Article : Google Scholar : PubMed/NCBI
22	Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K and Gilani AH: Isolation and structure elucidation of new nitrile and mustard oil glycosides from Moringa oleifera and their effect on blood pressure. J Nat Prod. 57:1256–1261. 1994. View Article : Google Scholar : PubMed/NCBI
23	Waiyaput W, Payungporn S, Issara-Amphorn J and Panjaworayan N: Inhibitory effects of crude extracts from some edible Thai plants against replication of hepatitis B virus and human liver cancer cells. BMC Complement Altern Med. 12:246–252. 2012. View Article : Google Scholar : PubMed/NCBI
24	Lipipun V, Kurokawa M, Suttisri R, Taweechotipatr P, Pramyothin P, Hattori M and Shiraki K: Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo. Antiviral Res. 60:175–180. 2003. View Article : Google Scholar : PubMed/NCBI
25	Murakami A, Kitazono Y, Jiwajinda S, Koshimizu K and Ohigashi H: Niaziminin, a thiocarbamate from the leaves of Moringa oleifera, holds a strict structural requirement for inhibition of tumor-promoter-induced Epstein-Barr virus activation. Planta Med. 64:319–323. 1998. View Article : Google Scholar : PubMed/NCBI
26	Sultana B, Anwar F and Ashraf M: Effect of extraction solvent/technique on the antioxidant activity of selected medicinal plant extracts. Molecules. 14:2167–2180. 2009. View Article : Google Scholar : PubMed/NCBI
27	Kumar V, Pandey N, Mohan V and Singh RP: Antibacterial and antioxidant activity of extract of Moringa oleifera leaves-An in vitro study. Int J Pharm Scis Rev Res. 12:89–94. 2012.
28	Ashok Kumar N and Pari L: Antioxidant action of Moringa oleifera Lam. (drumstick) against antitubercular drugs induced lipid peroxidation in rats. J Med Food. 6:255–259. 2003. View Article : Google Scholar : PubMed/NCBI
29	Gupta S Kumar, Kumar B, Srinivasan BP, Nag TC, Srivastava S, Saxena R and Aggarwal A: Retinoprotective effects of Moringa oleifera via antioxidant, anti-inflammatory, and anti-angiogenic mechanisms in streptozotocin-induced diabetic rats. J Ocul Pharmacol Ther. 29:419–426. 2013. View Article : Google Scholar : PubMed/NCBI
30	Jung IL: Soluble extract from Moringa oleifera leaves with a new anticancer activity. PLoS One. 9:e954922014. View Article : Google Scholar : PubMed/NCBI
31	Budda S, Butryee C, Tuntipopipat S, Rungsipipat A, Wangnaithum S, Lee JS and Kupradinun P: Suppressive effects of Moringa oleifera Lam pod against mouse colon carcinogenesis induced by azoxymethane and dextran sodium sulfate. Asian Pac J Cancer Prev. 12:3221–3228. 2011.PubMed/NCBI
32	Guevara AP, Vargas C, Sakurai H, et al: An antitumor promoter from Moringa oleifera Lam. Mutat Res. 440:181–188. 1999. View Article : Google Scholar : PubMed/NCBI
33	Dahiru D, Onubiyi JA and Umaru HA: Phytochemical screening and antiulcerogenic effect of Moringa oleifera aqueous leaf extract. African J Trad Complement Alternat Med. 3:70–75. 2006.
34	Peschel W, Sánchez-Rabaneda F, Diekmann W, et al: An industrial approach in the search of natural antioxidants from vegetable and fruit wastes. Food Chem. 97:137–150. 2006. View Article : Google Scholar
35	Siddhuraju P and Becker K: Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves. J Agric Food Chem. 51:2144–2155. 2003. View Article : Google Scholar : PubMed/NCBI
36	Hansen MB, Nielsen SE and Berg K: Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 119:203–210. 1989. View Article : Google Scholar : PubMed/NCBI
37	Tani TH, Khodursky A, Blumenthal RM, Brown PO and Matthews RG: Adaptation to famine: a family of stationary-phase genes revealed by microarray analysis. Proc Natl Acad Sci USA. 99:13471–13476. 2002. View Article : Google Scholar : PubMed/NCBI
38	Lotito SB and Fraga CG: Catechins delay lipid oxidation and alpha-tocopherol and beta-carotene depletion following ascorbate depletion in human plasma. Proc Soc Exp Biol Med. 225:32–38. 2000. View Article : Google Scholar : PubMed/NCBI
39	Hollingshead MG, Alley MC, Camalier RF, Abbott BJ, Mayo JG, Malspeis L and Grever MR: In vivo cultivation of tumor cells in hollow fibers. Life Sci. 57:131–141. 1995. View Article : Google Scholar : PubMed/NCBI
40	Alley MC, Hollingshead MG, Dykes DJ and Waud WR: Human tumor xenograft models in NCI drug developmentCancer Drug Discovery and Development: Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval. 72nd. Teicher BA and Andrews PA: Humana Press Inc; Totowa, NJ, USA: pp. 125–152. 2004
41	Plowman J, Dykes DJ, Hollingshead M, Simpson-Herren L and Alley MC: Human tumor xenograft models in NCI drug developmentAnticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval. Teicher B: Humana Press Inc; Totowa, NJ, USA: pp. 101–125. 1997, View Article : Google Scholar
42	Mi Q, Pezzuto JM, Farnsworth NR, Wani MC, Kinghorn AD and Swanson SM: Use of the in vivo hollow fiber assay in natural products anticancer drug discovery. J Nat Prod. 72:573–580. 2009. View Article : Google Scholar : PubMed/NCBI
43	Sahoo S, Raghavendra KM and Biswas S: Identification of a proteinaceous component in the leaf of Moringa Oleifera lam. with effects on high serum creatinine. Indian J Pharm Sci. 76:78–81. 2014.PubMed/NCBI
44	Parvathy M and Umamaheshwari A: Cytotoxic effect of Moringa oleifera leaf extracts on human multiple myeloma cell lines. Trends Med Res. 2:44–50. 2007. View Article : Google Scholar
45	Khalafalla MM, Abdellatef E, Dafalla HM, et al: Active principle from Moringa oleifera Lam leaves effective against two leukemias and a hepatocarcinoma. Afr J Biotechnol. 9:8467–8471. 2010.
46	Das BR, Kurup PA and Narasimha Rao PL: Antibiotic principle from Moringa pterygosperma. Naturwissenschaften. 41:661954. View Article : Google Scholar
47	Kær A, Malver O, El-menshawi B and Reischt J: Isothiocyanates in myrosinase-treated seed extracts of Moringa peregrine. Phytochemistry. 18:1485–1487. 1979. View Article : Google Scholar
48	Dayrit FM, Alcantar AD and Villasenor IM: Studies on Moringa oleifera seeds, Part I: The antibiotic compound and its deactivation in aqueous solution. Philipp J Sci. 119:23–32. 1990.
49	Eilert U: Antibiotic principles of seeds of Moringa oleifera. Indian Med J. 38:1013–1016. 1978.
50	Ghasi S, Nwobodo E and Ofili J: Hypocholesterolemic effects of crude extract of leaf of Moringa oleifera Lam. in high fat diet fed wistar rats. J Ethnopharmacol. 69:21–25. 2000. View Article : Google Scholar : PubMed/NCBI
51	Jaiswal D, Kumar Rai P, Kumar A, Mehta S and Watal G: Effect of Moringa oleifera lam. leaves aqueous extract therapy on hyperglycemic rats. J Ethnopharmacol. 123:392–396. 2009. View Article : Google Scholar : PubMed/NCBI
52	Edoga C, Njoku O, Amadi E and Okeke J: Blood sugar lowering effect of Moringa oleifera lam in albino rats. Int J Sci Technol. 3:88–90. 2013.
53	Muhammad AA, Pauzi NA, Arulselvan P, Abas F and Fakurazi S: In vitro wound healing potential and identification of bioactive compounds from Moringa oleifera Lam. Biomed Res Int. 2013:9745802013. View Article : Google Scholar : PubMed/NCBI
54	Guevara AP, Vargas C, Sakurai H, et al: An antitumor promoter from Moringa oleifera Lam. Mutat Res. 440:181–188. 1999. View Article : Google Scholar : PubMed/NCBI
55	Murakami A, Kitazono Y, Jiwajinda S, Koshimizu K and Ohigashi H: Niaziminin, a thiocarbamate from the leaves of Moringa oleifera, holds a strict structural requirement for inhibition of tumor-promoter-induced Epstein-Barr virus activation. Planta Med. 64:319–323. 1998. View Article : Google Scholar : PubMed/NCBI
56	Mi Q, Pezzuto JM, Farnsworth NR, Wani MC, Kinghorn AD and Swanson SM: Use of the in vivo hollow fiber assay in natural products anticancer drug discovery. J Nat Prod. 72:573–580. 2009. View Article : Google Scholar : PubMed/NCBI
57	Russell WM: The development of the three Rs concept. Altern Lab Anim. 23:298–304. 1995.PubMed/NCBI
58	Russell WM and Burch RL: The Principles of Humane Experimental Technique. Methuen; London, England: 1959
59	Suggitt M, Cooper PA, Shnyder SD and Bibby MC: The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare. Int J Oncol. 29:1493–1499. 2006.PubMed/NCBI
60	Lipinski CA: Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 44:235–249. 2000. View Article : Google Scholar : PubMed/NCBI
61	Teicher BA and Andrews PA: Part I: In vitro methodsAnticancer Drug Development Guide: Preclinical Screening, Clinical Trials and Approval. 2nd. Humana Press; Totowa, NJ, USA: pp. 3–78. 2004