Antitumor Mechanisms Of Potassium Piperate, A Derivative Of Mongolian Medicine Piper Longum L.

Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, the constituents extracted from the fruit of P. longum yielded piperine, pipernonaline, and piperlonguminine. However, the antitumor properties of these constituents are not understood at all. We found that potassium piperate (GBK), a derivative of piperine,has ability to inhibit proliferation of cancer cells, especially mammary cancer cells. It also selectively inhibits the G1-S-phase transition in mammary cancer cells. Induction of G1 arrest by GBK is correlated with induction of CDK inhibitor p27 expression as well as inhibition of cyclin E, cyclin A and cyclin B. Moreover, mini-chromosome maintenance (MCM) proteins are markedly down-regulated in MCF-7 cells treated with GBK. On the other hand, GBK selectively kills cancer cells by targeting the stress response to ROS. GBK might also inhibit cancer cell proliferation through epigenetic signaling pathways. Altogether, these results show GBK possesses potential anti-cancer activity against mammary cancer cells by inhibiting cell proliferation and promoting cell apoptosis.