Colorectal cancer is among four most common malignancies and the second leading cause of cancer death in the western world. Although the standard treatment regimens have improved the prognosis, resistance to cytotoxic chemotherapy is still a common problem in these patients and a major obstacle to effective treatment of disseminated neoplasms. The subject of this study was to evaluate a possible role of anthocyanidins, natural products belonging to the group of flavonoids, in the treatment of colorectal cancer. Primary (CACO-2) and metastatic human colorectal carcinoma cell lines (LoVo and LoVo ADR) were used to test different aspects of their pharmacological effect, such as their ability to affect cancer cell growth and to modulate the cytotoxicity of certain well established anticancer drugs. Their proapototic properties, as well as their capacity to induce changes in the cellular redox status and modulate drug transport mechanisms were also explored.
The anthocyanidins used in this study, delphinidin and cyanidin, demonstrated strong cytotoxic effect in metastatic human colorectal cancer cell lines, LoVo and LoVo ADR, and were able to modulate the cytotoxicity of camptothecin, drug used in most colorectal cancer treatment regimes. Although well known for their antioxidant properties and lower toxicity in normal cells, delphinidin and cyanidin showed strong prooxidant activity in the metastatic colon carcinoma cell lines. We show that anthocyanidins inactivate the glutathione antioxidant system thus promoting oxidative stress in these cells, which might be responsible for their proapoptotic activity. Moreover, when applied at low, non-cytotoxic concentrations over a long period of time, they also affect anticancer drug transport across cell membranes by modulating expression of certain transport proteins (ABC transporters). These results suggest that anthocyanidins can be good candidates for improving colorectal cancer therapy and warrant new investigation on their activity.
