Anti-Tumor Effect of Pinus massoniana Bark Proanthocyanidins on Ovarian Cancer through Induction of Cell Apoptosis and Inhibition of Cell Migration.

Jia Liu,Ershao Zhang,Dachang Wu,Jing Wang,Jing Bai,Xinli Li,Guoqiang Jiang,Lawrence Owusu,Weiling Li,Yi-Hsien Hsieh

doi:10.1371/journal.pone.0142157

Abstract

Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties. Here, we investigated the anti-tumor effect of PMBPs on ovarian cancer. The results indicated that PMBPs significantly reduced the growth of ovarian cancer cells and induced dose-dependent apoptosis. The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway. In addition, wound healing and transwell chamber assays revealed that PMBPs could suppress migration and invasion of ovarian cancer cells. PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK. Our findings suggest that PMBPs has the potential to be developed as an anti-tumor drug for ovarian cancer treatment and/ or disease management.

Highlights

Ovarian cancer remains the fifth most common type of cancer in females and the leading cause of death in gynecologic malignancies [1].The first-line treatment of ovarian cancer is usually traditional surgery combined with platinum-paclitaxel based chemotherapy [2]
We explored the potential utility of proanthocyanidins from Pinus massoniana bark on ovarian cancer cells in the quest of finding novel effective drugs for ovarian cancer treatment
Our data here demonstrated that Pinus massoniana bark proanthocyanidins (PMBPs) reduced the proliferation, induced apoptosis and suppressed the migration of ovarian cancer cells

Summary

Introduction

Ovarian cancer remains the fifth most common type of cancer in females and the leading cause of death in gynecologic malignancies [1].The first-line treatment of ovarian cancer is usually traditional surgery combined with platinum-paclitaxel based chemotherapy [2]. Despite the good initial response in most ovarian cancer patients, the 5-year survival rate is still low due to relapses- a common occurrence after first line treatment [3]. There have been few developments in ovarian cancer treatment since the standardization of cisplatin and paclitaxel drugs in the last 20 years [4]. There is an urgent need to develop novel effective drugs for ovarian cancer treatment. Some natural bioactive phytochemical are used to impede proliferation or metastasis of cancer cells [5]. Such phytochemical are non-toxic and devoid of side effects, they are good alternatives and/ or complementary to conventional cytotoxic chemotherapy [5].

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Results

Conclusion