Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

Li-Hua Gong,Jian-Ge Qiu,Qi-Wei Jiang,Shi-Shi Pan,Xiao-Jian Yan,Huan Wang,You-Qiu Xue,Xiao-Long Mei,Fei-Yun Zheng,Wu-Ming Qin,Zhi Shi,Xiu-Xiu Chen

doi:10.1155/2014/906804

Abstract

Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.

Highlights

Ovarian cancer is the most lethal cancer of female reproductive tract, accounting for ∼16,000 deaths annually [1].The high mortality results partially from the nonspecific and commonly misinterpreted symptoms associated with the disease
We firstly demonstrated that PL selectively mediated time- and concentration-dependent antigrowth effects on human ovarian cancer cells
Synergistically enhanced the antigrowth effect of DDP or TX, which suggested that PL might be a potential chemosensitizer for ovarian cancer chemotherapy

Summary

Introduction

Ovarian cancer is the most lethal cancer of female reproductive tract, accounting for ∼16,000 deaths annually [1]. A role for chronic oxidative stress has been proposed in the etiology of malignant transformation and elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells [8, 9]. Carbonyl reductase 1, known to regulate oxidative stress by modulating redox and ROS homeostasis [18]. Consistent with this theory, when PL interacted directly with GSTP1, protein glutathionylation was identified as a process associated with cellular toxicity [19]. We firstly demonstrate that PL selectively inhibited cell growth and induced ROS-dependent cell apoptosis and G2/M cell cycle arrest in human ovarian cancer. Our results provide new drug therapeutic potential of PL on human ovarian cancer

Materials and Methods

PL Selectively Inhibited the Growth of Ovarian Cancer

PL Synergized with DDP or TX in OVCAR3 Ovarian

Discussion