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Vitamin C induces apoptosis in human colon cancer cells through endoplasmic reticulum stress and mitochondrial pathway

It has been reported that vitamin C plays an effective role in the treatment and prevention of cancer, but its specific mechanism is still not fully understood. In particular, the effect of vitamin C on the treatment and prevention of colorectal cancer, which has been increasingly a common disease in South Korea due to westernized diet of many Koreans, is still largely unknown. Therefore, we have examined the effects of vitamin C on the induction of apoptosis on HCT-8, human colon cancer cell line. We have first confirmed that the optimal concentrations of vitamin C for the induction of apoptosis on human colon cancer cell line, HCT-8 is 2 mM of vitamin C. Here we demonstrated that vitamin C induced ER stress through redox imbalance as antioxidant and, increased cytosol calcium level. Then, we investigated the changes of ER-stress induced molecules. As a result, the phosphorylation of pro-apoptotic protein, Bad decreased and Bad, which was subsequently released from 14-3-3, was translocated to the mitochondria. In addition, we also found that the vitamin C increased expression of pro-apoptotic protein, Bax and tumor suppressor gene product, p53, which usually resulted in apoptosis, in a time dependent manner. Moreover, we have witnessed that vitamin C treatment disrupts mitochondrial membrane potential in HCT-8, human colon cancer cell line. Taken together, vitamin C induced redox imbalance, resulting in apoptosis in human colon cancer cells by both endoplasmic reticulum stress and Bad/p53/Bax-mediated activation of mitochondrial pathway.

Published on 09-04-2009
Authors: Jee Eun Kim, Jae Seung Kang, Da Jung Jung, Eunsil Hahm, Seung Koo Lee, Se Yeon Bae, Young Il Hwang, Dong Hoon Shin and Wang Jae Lee
Source: The Journal of Immunology, 2007, 178, 49.25