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

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.

Recent Advances in Anticancer Activities and Drug Delivery Systems of Tannins

“…PAs could induce cell apoptosis in various cancers, at least in part, via inhibiting the activation of PI3K/AKT signaling pathway, reducing expression of antiapoptotic proteins, and increasing expression of pro‐apoptotic proteins . For example, a cranberry‐derived PA extract (CDPA, 50 μg/mL) could induce caspase‐independent cell death via autophagy and low levels of apoptosis in acid‐sensitive human esophageal adenocarcinoma (EAC) JHAD1 and OE33 cells but cause cellular necrosis in acid‐resistant EAC OE19 cells, which was involved in the inhibition of PI3K/AKT/mTOR and MAPK signaling pathway, induction of pro‐apoptotic protein (deamidated Bcl‐xL, Bax, Bak1, cytochrome c, and PARP) and cell cycle arrest in G2/M phase .…”

“…PAs also exhibited anticancer activity via antiinvasion and antimetastasis property as well as antiangiogenesis in a variety of cancers, which was mainly mediated by inhibiting the epithelial‐to‐mesenchymal transition (EMT), the activity of NF‐κB, MMP‐9, epidermal growth factor receptor (EGFR), and so on . For instance, GSP has been investigated to inhibit the cigarette smoke condensate (CSC) induced cell migration in non‐small‐cell lung cancer (NSCLC) cells via reducing oxidative stress levels and the EMT, which not only reversed the CSC‐induced increase in the expression level of p47(phox) and p33(phox), but also reduced the binding between p47(phox) and p33(phox) proteins .…”

“…In addition, GSP could suppress the migration, MMP‐2/9 secretion, and tube formation of HMEC‐1 cells in a dose‐dependent manner and inhibit the neovascularization in chick chorioallantoic membrane angiogenesis assay in a dose‐dependent manner, which was mediated by inhibiting the phosphorylation of tyrosine kinase and VEGF receptor 2 as well as ERK1/2 . Furthermore, CDPA could also inhibit the PI3K/AKT signaling in ovarian cancer cells as well as in endothelial cells and block the function of VEGF to suppress the endothelial tube formation, while PAs from Pinus massoniana bark could inhibit the migration and invasion ability of ovarian cancer cells via suppressing the activity of NF‐κB or ERK1/2 and p38MAPK resulting in inhibition of MMP‐9 activity . Differently, another study has demonstrated that GSP suppress melanoma cell migration through decreasing the expression of prostaglandin E2 receptors (EP2 and EP4) followed by reducing cellular accumulation of β‐catenin, which was also mediated by the suppressive activity of MMP‐2/9, MITF, and PI3K/p‐AKT .…”

Paris polyphylla extract inhibits proliferation and promotes apoptosis in A549 lung cancer cells

“…They are a family of cysteine proteases involved in regulation of apoptosis, which is considered to be a key to cancer cell death [14][15][16][17]. In this study, PPE treatment led to significantly lowered expression of Bcl-2, and significant increases in the expression of caspase-9.…”

Pinus massoniana bark extract inhibits migration of the lung cancer A549 cell line

“…Overexpression of MMPs is frequently detected in various types of cancer and has been observed to facilitate tumor cell metastasis (11). Therefore, the inhibition of the activities of MMPs in the ECM may prevent the invasion of tumor cells and form the basis for an efficient anticancer therapy.Pinus massoniana is a tree species native to Southern China (12) and P. massoniana bark extract (PMBE) is an established traditional Chinese medicine used for the treatment of rheumatism, arthralgia, inflammation and cancer (13,14). The primary active component of PMBE is anthocyanin series B (15).…”