Grape seed proanthocyanidins (GSPs) inhibit the growth of cervical cancer by inducing apoptosis mediated by the mitochondrial pathway.

Qing Chen,Peng-Sheng Zheng,Xiao-Fang Liu,Burton B. Yang

doi:10.1371/journal.pone.0107045

Abstract

Grape seed proanthocyanidins (GSPs), a biologically active component of grape seeds, have been reported to possess a wide array of pharmacological and biochemical properties. Recently, the inhibitory effects of GSPs on various cancers have been reported, but their effects on cervical cancer remain unclear. Here, we explored the effect of GSPs on cervical cancer using in vitro and in vivo models. In vitro, the treatment of HeLa and SiHa cells with GSPs resulted in a significant inhibition of cell viability. Further investigation indicated that GSPs led to the dose-dependent induction of apoptosis in cancer cells. The underlying mechanism was associated with increased expression of the pro-apoptotic protein Bak-1, decreased expression of the anti-apoptotic protein Bcl-2, the loss of mitochondrial membrane potential, and the activation of caspase-3, suggesting that GSPs induced cervical cancer cell apoptosis through the mitochondrial pathway. In addition, the administration of GSPs (0.1%, 0.2%, and 0.4%, w/v) as a supplement in drinking water significantly inhibited the tumor growth of HeLa and SiHa cells in athymic nude mice, and the number of apoptotic cells in those tumors was also increased significantly. Taken together, our studies demonstrated that GSPs could inhibit the growth of cervical cancer by inducing apoptosis through the mitochondrial pathway, which provides evidence indicating that GSPs may be a potential chemopreventive and/or chemotherapeutic agent for cervical cancer.

Highlights

Cervical cancer is the third most common cancer [1] and the fourth leading cause of cancer-related death among women worldwide [2]
The results showed that the treatment of both HeLa and SiHa cells with Grape seed proanthocyanidins (GSPs) for 48 h resulted in significant increase in caspase-3 activity in a dosedependent manner (Fig. 5E and F), suggesting that the apoptosis of cervical cancer cells induced by GSPs occurred through the activation of the caspase-3 pathway
Using the MTT assay, we found that the treatment of HeLa and SiHa cells with GSPs resulted in a dose-dependent reduction in cell viability (Fig. 1A and B)

Summary

Introduction

Cervical cancer is the third most common cancer [1] and the fourth leading cause of cancer-related death among women worldwide [2]. 80% of cervical cancer cases occur in developing countries, where approximately 529,000 new cases are detected every year, with nearly half of these patients dying [3]. Due to the lack of screening and reduced access to appropriate therapeutic facilities and drugs, the incidence and mortality rates of cervical cancer rank second after breast cancer [4]. Many cases have developed into invasive cervical cancers at the time of diagnosis, and the patients are no longer candidates for radical surgical therapy. Chemotherapy and radiotherapy are still the major treatments for invasive cervical cancer, the five-year survival rate is limited because of the limited efficacy and high toxicity of many anticancer drugs. The exploration and development of more effective and less toxic therapeutic agents are required

Methods

Results

Conclusion