The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis

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),...

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Veröffentlicht in:Oncotarget 2017-07, Vol.8 (29), p.47250-47268
Hauptverfasser: Fan, Lifei, Cao, Xuemin, Yan, Huijuan, Wang, Qian, Tian, Xiaoxia, Zhang, Lan, He, Xiaoyan, Borjihan, Gereltu, Morigen
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container_end_page 47268
container_issue 29
container_start_page 47250
container_title Oncotarget
container_volume 8
creator Fan, Lifei
Cao, Xuemin
Yan, Huijuan
Wang, Qian
Tian, Xiaoxia
Zhang, Lan
He, Xiaoyan
Borjihan, Gereltu
Morigen
description 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.
doi_str_mv 10.18632/oncotarget.16872
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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. 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subjects Animals
Antineoplastic Agents, Phytogenic - chemical synthesis
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival
Cisplatin - pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Synergism
Etoposide - pharmacology
Female
G1 Phase Cell Cycle Checkpoints - drug effects
Humans
Hypolipidemic Agents - chemical synthesis
Hypolipidemic Agents - pharmacology
MCF-7 Cells
Mice
Piperidines - chemical synthesis
Piperidines - pharmacology
Reactive Oxygen Species - metabolism
Research Paper
Stress, Physiological
Xenograft Model Antitumor Assays
title The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis
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