Anticancer Activity of (±)-Kusunokinin Derivatives towards Cholangiocarcinoma Cells

This study aimed to investigate the cytotoxicity and anticancer activity of (+/-)-kusunokinin derivatives ((+/-)-TTPG-A and (+/-)-TTPG-B). The cytotoxicity effect was performed on human cancer cells, including breast cancer, cholangiocarcinoma, colon and ovarian cancer-cells, compared with normal cells, using the MTT assay. Cell-cycle arrest and apoptosis were detected using flow-cytometry analysis. We found that (+/-)-TTPG-B exhibited the strongest cytotoxicity on aggressive breast-cancer (MDA-MB-468 and MDA-MB-231) and cholangiocarcinoma (KKU-M213), with an IC50 value of 0.43 +/- 0.01, 1.83 +/- 0.04 and 0.01 +/- 0.001 mu M, respectively. Interestingly, (+/-)-TTPG-A and (+/-)-TTPG-B exhibited less toxicity than (+/-)-kusunokinin (9.75 +/- 0.39 mu M) on L-929 cells (normal fibroblasts). Moreover, (+/-)-TTPG-A predominated the ell-cycle arrest at the S phase, while (+/-)-TTPG-B caused cell arrest at the G0/G1 phase, in the same way as (+/-)-kusunokinin in KKU-M213 cells. Both (+/-)-TTPG-A and (+/-)-TTPG-B induced apoptosis and multi-caspase activity more than (+/-)-kusunokinin. Taken together, we conclude that (+/-)-TTPG-A and (+/-)-TTPG-B have a strong anticancer effect on cholangiocarcinoma. Moreover, (+/-)-TTPG-B could be a potential candidate compound for breast cancer and cholangiocarcinoma in the future.

Automated summary

This study investigated the cytotoxicity and anticancer activity of (+/-)-kusunokinin derivatives on various cancer cells. The results showed that (+/-)-TTPG-B exhibited the strongest cytotoxicity on breast cancer and cholangiocarcinoma cells. Both (+/-)-TTPG-A and (+/-)-TTPG-B induced cell cycle arrest and apoptosis, and their effects were superior to (+/-)-kusunokinin.