The anti-cancer and anti-mutagenic properties of anthocyanins are directly linked to their antioxidant properties. Epidemiological studies have linked the consumption of fruits and vegetables, rich in polyphenols, to a lower cancer risk. For example, elderly men in France, who consume the typical Mediterranean diet with high amounts of vegetables, fruits, nuts, olive oil and also red wine, have a 75% lower risk of developing prostate cancer than their counterparts in the United States. Many studies have shown the anti-cancer and anti-mutagenic of cyanidin and its non-toxic properties towards normal cells . These studies used cyanidin glycosides extracted from a wide range of foods such as black rice, mulberries, bilberries and blackberries. In-vivo and in-vitro studies have linked cyanidin to reduced risk of leukemia, lung cancer colon cancer, skin cancer and prostate cancer [1,2,3,4,5]. Feng et al extracted cyanidin 3-rutinoside from black raspberries and found that this cyanidin glycoside killed cultured leukemia cells in a dose-dependent manner . The phytochemical induced apoptosis by increasing the level of peroxides and activated mitogen-activated protein kinases, which activate the mitochondrial pathway mediated by Bim. Cyanidin 3-rutinoside showed no cytotoxic effects to normal cells, indicating that it could be used as a potential drug in leukemia therapy.
An in-vivo study with rodents showed that cyanidin 3-glucoside and a bilberry extract, containing high levels of cyanidin-3-glucoside, reduced the formation of intestinal adenoma by up to 45% in a mouse model of human familial adenomatous polyposis . Adenomas are growths that could progress into carcinomas. The researchers here also concluded that cyanidin and anthocyanins in general should be further investigated chemopreventive agents against human colon cancer. Another study found that cyanidin 3-glycoside protects colon cancer cells against oxidative DNA damage in vitro but that it exerted no antioxidant affect at nutritionally relevant levels in vivo . Addition of cyanidin-3-glycoside to a vitamin E deficient diet (less than 0.5 mg/kg vitamin E) did not inhibit the lipid peroxidation or DNA damage in rats. Vitamin E deficiency resulted in a significant increase in lipid peroxidation in plasma, liver and red cells. Briviba et al. demonstrated the protective effect of cyanidin, but not its glycosides, on cultured colon cancer cells . Cyanidin inhibited the mitogen-induced metabolic activity, reduced free intracellular calcium and inhibited growth of the colon carcinoma cells. Neurotensin and epidermal growth factor (EGF) have been associated with colon cancer. Cyanidin was able inhibit the increase of intracellular calcium induced by neurotensin. The epidermal growth factor acts by binding to receptor on the cell surface and stimulating the intrinsic protein-tyrosine kinase activity, which in turns, initiates a signal transduction cascade. This results in biochemical changes within the cell, such as rise in intracellular calcium levels, increased glycolysis and protein synthesis that ultimately lead to cell proliferation. Cyanidin reduced the metabolic activity and reduced the cell growth .
A study with human vulva cancer cells also confirmed the inhibitory action of cyanidin on overexpressing of the EGF receptor. The cell growth and tyrosine kinase activity of the EGF receptor were inhibited by cyanidin and delphinidin. The aglycones malvidin and the glycones cyanidin 3-beta-D-galactoside and malvidin 3-beta-D-glucoside were not that active. Cyanidin and delphine inhibited downstream signaling cascades by inhibiting the activation of a cancer-promoting fusion protein .
Ding et al found that cyanidin glycoside inhibits the proliferation of cultured lung carcinoma cells and migration and invasion epithelial carcinoma cells of in nude mice . Chen et al isolated the anthocyanins cyanidin 3-glucoside and peonidin 3-glucoside from black rice and tested their effects on different cancer cell lines. They found that the breast cancer cell line HS578T was the most sensitive to the two phytochemicals and experienced the strongest inhibition of cell growth. Cyanidin 3-glucoside decreased the levels of cyclin-dependent kinases (CDK-1 and CDK-2) and cyclins (B1and D1). Cyanidin also induced activation of the effector caspase CASP3, which cleaves proteins resulting in cell death . Hyun et al. also tested the effects of anthocyanins extracted from black rice on the growth of cancer cells. Canidin and maldivin, showed a significant inhibition of the growth of human monocytic leukemia cells and caused cell cycle arrest and apoptosis .
The protective effects of cyanidin and kaempferol, both present in red wine, were investigated by Muñoz-Espada and Watkins. They tested the influence of these phytochemicals on cultured prostate cancer cells and came to the conclusion that cyanidin and kaempferol reduced the production of cyclooxygenases-2 by mediating the actions of the nuclear factor kappaB and peroxisome proliferator-activated receptor gamma .
The main cyanidin glycosides in mulberry are cyanidin 3-rutinoside and cyanidin 3-glucoside. Chen et al found that these cyanidin glycosides had an inhibitory effect on the migration and invasion of human lung cancer cells, without showing cytotoxicity. The cyanidin glycosides acted by decreasing the expression of matrix metalloproteinase-2 and urokinase-plasminogen activator and increased the expression of the tissue inhibitor of matrix matalloprotinase-2 and plasminogen activator inhibitor. An in-vitro study with human melanoma cells demonstrated that cyanidin 3-O-beta-glucopyranoside was able to reverse the cancer cells from proliferating to the differentiated state. Treatment of the cancer cells with this anthocyanin decreased cell proliferation, without inducing apoptosis. This study concluded that cyanidin 3-O-beta-glucopyranoside is a potential molecule for the treatment of melanoma .
 Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H, Yin XM. " Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress." J Biol Chem. 2007 May 4;282(18):13468-76.
 Cooke D, Schwarz M, Boocock D, Winterhalter P, Steward WP, Gescher AJ, Marczylo TH. " Effect of cyanidin-3-glucoside and an anthocyanin mixture from bilberry on adenoma development in the ApcMin mouse model of intestinal carcinogenesis--relationship with tissue anthocyanin levels." Int J Cancer. 2006 Nov 1;119(9):2213-20.
 Ding M, Feng R, Wang SY, Bowman L, Lu Y, Qian Y, Castranova V, Jiang BH, Shi X. " Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity." J Biol Chem. 2006 Jun 23;281(25):17359-68.
 Chen PN, Chu SC, Chiou HL, Chiang CL, Yang SF, Hsieh YS. " Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo." Nutr Cancer. 2005;53(2):232-43.
 Muñoz-Espada AC, Watkins BA. "Cyanidin attenuates PGE2 production and cyclooxygenase-2 expression in LNCaP human prostate cancer cells." J Nutr Biochem. 2006 Sep;17(9):589-96.
 Fimognari C, Berti F, Nüsse M, Cantelli-Fortii G, Hrelia P. " In vitro anticancer activity of cyanidin-3-O-beta-glucopyranoside: effects on transformed and non-transformed T lymphocytes." Anticancer Res. 2005 Jul-Aug;25(4):2837-40
 Chen PN, Chu SC, Chiou HL, Kuo WH, Chiang CL, Hsieh YS. "Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line." Cancer Lett. 2006 Apr 28;235(2):248-59.
 Serafino A, Sinibaldi-Vallebona P, Lazzarino G, Tavazzi B, Rasi G, Pierimarchi P, Andreola F, Moroni G, Galvano G, Galvano F, Garaci E. " Differentiation of human melanoma cells induced by cyanidin-3-O-beta-glucopyranoside." FASEB J. 2004 Dec;18(15):1940-2.
 Duthie SJ, Gardner PT, Morrice PC, Wood SG, Pirie L, Bestwick CC, Milne L, Duthie GG. "DNA stability and lipid peroxidation in vitamin E-deficient rats in vivo and colon cells in vitro--modulation by the dietary anthocyanin, cyanidin-3-glycoside." Eur J Nutr. 2005 Jun;44(4):195-203.
 Hyun JW, Chung HS. " Cyanidin and Malvidin from Oryza sativa cv. Heugjinjubyeo mediate cytotoxicity against human monocytic leukemia cells by arrest of G(2)/M phase and induction of apoptosis."J Agric Food Chem. 2004 Apr 21;52(8):2213-7.
 Briviba K, Abrahamse SL, Pool-Zobel BL, Rechkemmer G. "Neurotensin-and EGF-induced metabolic activation of colon carcinoma cells is diminished by dietary flavonoid cyanidin but not by its glycosides." Nutr Cancer. 2001;41(1-2):172-9.
 Meiers S, Kemény M, Weyand U, Gastpar R, von Angerer E, Marko D. "The anthocyanidins cyanidin and delphinidin are potent inhibitors of the epidermal growth-factor receptor." J Agric Food Chem. 2001 Feb;49(2):958-62.