The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis
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Lifei Fan1,*, Xuemin Cao1,*, Huijuan Yan1,*, Qian Wang1, Xiaoxia Tian1, Lan Zhang1, Xiaoyan He1, Gereltu Borjihan2 and Morigen1
1School of Life Sciences, Inner Mongolia University, Hohhot 010021, P.R. China
2Institute of Macromolecular Chemistry and Mongolian Medicine, Inner Mongolia University, Hohhot 010021, P.R. China
*These authors have contributed equally to this work
Morigen, email: firstname.lastname@example.org
Lifei Fan, email: email@example.com
Keywords: antihyperlipidemic drug, potassium piperate, G1-S-phase transition, apoptosis, breast cancer
Received: October 26, 2016 Accepted: March 14, 2017 Published: April 12, 2017
Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK), a derivative of piperine, inhibited proliferation of cancer cells. GBK selectively inhibited the G1-S-phase transition in breast cancer cells and the G1 arrest was correlated with induction of p27 expression, which is an inhibitor for cyclin-dependent kinases, and inhibition of cyclin A, cyclin E and cyclin B expression. Moreover, GBK treatment led to a downregulation of the mini-chromosome maintenance protein expression and induction of mitochondrial-dependent cell apoptosis in breast cancer cells. Our results also suggested that GBK might also inhibit cancer cell proliferation through epigenetic signaling pathways. A synergistic effect in inhibition of cancer cell proliferation was found when GBK was combined with chemotherapy medicines etoposide phosphate or cisplatin at middle or low doses in vitro. These results show that GBK is a novel potential anti-breast cancer drug that inhibits cell proliferation and promotes cell apoptosis.
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