In vitro and in vivo antitumour effects of coconut water vinegar on 4T1 breast cancer cells
Background: Coconut water and vinegars have been reported to possess potential anti-tumour and immunostimulatory effects. However, the anti-tumour, anti-inﬂammatory and immunostimulatory effects of coconut water vinegar have yet to be tested.
Objective: This study investigated the in vitro and in vivo anti-tumour effects of coconut water vinegar on 4T1 breast cancer cells. Methods: The 4T1 cells were treated with freeze-dried coconut water vinegar and subjected to MTT cell viability, BrdU, annexin V/PI apoptosis, cell cycle and wound healing assays for the in vitro analysis. For the in vivo chemopreventive evaluation, mice challenged with 4T1 cells were treated with 0.08or 2.00 mL/kg body weight of fresh coconut water vinegar for 28 days. Tumour weight, apoptosis of tumour cells, metastasis and immunity of untreated mice and coconut water vinegar-treated 4T1 challenged mice were compared.
Results: Freeze-dried coconut water vinegar reduced the cell viability, induced apoptosis and delayed the wound healing effect of 4T1 cells in vitro. In vivo, coconut water vinegar delayed 4T1 breast cancer progression in mice by inducing apoptosis and delaying the metastasis. Furthermore, coconut water vinegar also promoted immune cell cytotoxicity and production of anticancer cytokines. The results indicate that coconut water vinegar delays breast cancer progression by inducing apoptosis in breast cancer cells, suppressing metastasis and activating anti-tumour immunity.
Conclusion: Coconut water vinegar is a potential health food ingredient with a chemopreventive effect.
- Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87–108.
- Davies NJ, Batehup L, Thomas R. The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature. Br J Cancer 2011; 105: S52–73.
- Bhoo-Pathy N, Hartman M, Yip CH, Saxena N, Taib NA, Lim SE, et al. Ethnic differences in survival after breast cancer in South East Asia. Plos One 2012; 7: e30995.
- Potischman N, Swanson CA, Coates RJ, Gammon MD, Brogan DR, Curtin J, et al. Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer. Int J Cancer 1999; 30: 315–21.
- Mandal MD, Mandal S. Coconut (Cocos nucifera L.: Arecaceae): In health promotion and disease prevention. Asian Pac J Trop Dis 2011; 4: 241–7.
- Yong JWH, Ge L, Ng YF, Tan SN. The chemical composition and biological properties of coconut (Cocos nucifera L.) water. Molecules 2009; 14: 5144–64.
- Geetha V, Bhavana KP, Chetana R, Gopala Krishna AG, Suresh Kumar G. Studies on the composition and in vitro antioxidant activities of concentrates from coconut testa and tender coconut water. J Food Process Technol 2016; 7: 588.
- Christina YI, Ibrahim M, Rifa’I M. Polyherbal EMSA ERITIN blocks nuclear factor-kappa B (NF-kB) and proinflammatory cytokines in irradiated mice. Am J Immunol 2015; 11: 17–25.
- Prabhu S, Dennison SR, Mura M, Lea RW, Snape TJ, Harris F. Cn-AMP2 from green coconut water is an anionic anticancer peptide. J Pept Sci 2014; 20: 909–15.
- Wang D, DuBois RN. Immunosuppression associated with chronic inflammation in the tumor microenvironment. Carciongenesis 2015; 36: 1085–93.
- Oquntoyinbo FA, Fusco V, Cho GS, Kabisch J, Neve H, Bockelmann W. Produce from Africa’s gardens: potential for leafy vegetable and fruit fermentations. Front Microbiol 2016; 7: 981.
- Budak NH, Aykin E, Seydim AC, Greene AK, Guzel-Seydim Z. Functional properties of vinegar. J Food Sci 2014; 79: R757–64.
- Samad A, Azlan A, Ismail A. Therapeutic effects of vinegar: a review. Curr Opin Food Sci 2016; 8: 56–61.
- Sun X, Hu M, Henrik M, Helen SE, Dai D, Duan W, et al. Risk factors for oesophageal cancer in Linzhou, China: a case control study. Asian Pacific J Cancer Prev 2003; 4: 119–24.
- Baba N, Higashi Y, Kanekura T. Japanese black vinegar ‘Izumi’ inhibits the proliferation of human squamous cell carcinoma cells via necroptosis. Nutr Cancer 2013; 65: 1092–7.
- Shimoji Y, Kohno H, Nanda K, Nishikawa Y, Ohigashi H, Uenakai K, et al. Extract of Kurosu, a vinegar from unposlihed rice, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Nutr Cancer 2004; 49: 170–3.
- Mimura A, Suzuki Y, Toshima Y, Yazaka S, Ohtsuki T, Ui S, et al. Induction of apoptosis in human leukemia cells by naturally fermented sugar cane vinegar (kibizu) of Amami Ohshima Island. BioFactors 2004; 22: 93–7.
- Guo XK, Wang TJ, Gu JF. Effect of esophageal cancer- and stomach cancer-preventing vinegar on N-nitrosoproline formation in the human body. World J Gastroenterol 1997; 3: 269–70.
- Nishidai S, Nakamura Y, Torikai K, Yamamoto M, Ishihara N, Mori H, et al. Kurosu, a traditional vinegar produced from unpolished rice, suppresses lipid peroxidation in vitro and in mouse skin. Biosci Biotechnol Biochem 2000; 64:1909–14.
- Mohamad N., Yeap S, Lim K, Yusof H, Beh B, Tan S, et al. Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice. Chinese Medicine 2015; 10: 3.
- Yeap SK, Mohd Yusof H, Mohamad NE, Beh BK, Ho WY, Ali NM, et al. In vivo immunomodulation and lipid peroxidation activities contributed to chemoprevention effects of fermented mung bean against breast cancer. Evid Based Complementary Altern Med 2013; 2013: 708464.
- Mohamad NE, Yeap SK, Ky H, Ho WY, Boo SY, Chua J, et al. Dietary coconut water vinegar for improvement of obesity-associated inflammation in high-fat-diet-treated mice. Food Nutr Res 2017;61:1368322.
- Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, et al. In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice. Drug Des Dev Ther 2015; 9: 1401–17.
- Wright SC, Bonavida B. YAC-1 variant clones selected for resistance to natural killer cytotoxic factors are also resistant to natural killer cell-mediated cytotoxicity. Proc Natl Acad Sci USA 1983; 80: 1688–92.
- Glade MJ. Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition 1999; 15: 523–6.
- Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, et al. Cancer prevention with natural compounds. Semin Oncol 2010; 37: 258–81.
- Nanda K, Miyoshi N, Nakamura Y, Shimoji Y, Tamura Y, Nishikawa Y, et al. Extract of vinegar ‘Kurosu’ from unpolished rice inhibits the proliferation of human cancer cells. J Exp Clin Cancer Res 2004; 23: 69–75.
- Garte SJ. The c-myc oncogene in tumor progression. Crit Rev Oncog 1993; 4: 435–49.
- Heppner GH, Miller FR, Shekhar PVM. Nontransgenic models of breast cancer. Breast Cancer Res 2000; 2: 331–4.
- Wenzel J, Zeisig R, Fichtner I. Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cells-platelet interactions. Clin Exp Metastasis 2010; 27: 25.
- Dhaheri YA, Attoub S, Arafat K, AbuQamar S, Viallet J, Saleh A, et al. Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NFkB signaling and reduction of nitric oxide production. Plos One 2013; 8: e68808.
- Arias-Salvatierra D, Silbergeld EK, Acosta-Saavedra LC, Calderon-Aranda ES. Role of nitric oxide produced by iNOS through NF-kB pathway in migration of cerebellar granule neurons induced by lipopolysaccharide. Cell Sign 2011; 23: 425–35.
- Yerlikaya A, Okur E, Ulukaya E. The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib. Tumor Biol 2012; 33: 1385–92.
- Christina YI, Ibrahim M, Rifa’I M. Polyherbal EMSA ERITIN blocks nuclear factor-kapppa B (NF-kB) and proinflammatory cytokines in irradiated mice. Am J Immunol 2015; 11: 17–25.
- Mohamad NE, Yeap SK, Lim KL, Yusof HM, Beh BK, Tan SW, et al. Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice. Chin Med 2015; 10: 3.
- Kano A. Tumor cell secretion of soluble factor(s) for specific immunosuppression. Sci Rep 2015; 5: 8913.
- Cha E, Graham L, Manjili MH, Bear HD. IL-7+IL-15 are superior to IL-2 for the ex vivo expansion of 4T1 mammary carcinoma-specific T cells with greater efficacy against tumors in vivo. Breast Cancer Res Treat 2010; 122: 359–69.
This work is licensed under a Creative Commons Attribution 4.0 International License
Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation.