Study On Anti-cancer Effect Of Polydatin And The Underlying Mechanism

Cancer has become an increasing health threat worldwide as a result of populationaging and growth as well as adoption of cancer-associated lifestyle. Breast cancer is themost frequently diagnosed cancer and the leading cause of cancer death among women.Lung cancer is the most commonly diagnosed cancer and the leading cause of cancerdeath in men. Despite advances in all the standard treatments, such as surgery,radiotherapy, chemotherapy, molecular targeting therapy, or combined regiment, theoverall outcome is still poor due to metastasis, drug resistance, and recurrence. Thus thequest to find novel agents for cancer therapy is a never-ending venture.With development of phytochemistry, more and more researchers pay theirattention to the importance of herbal plants． Famous examples of plant-basedtherapeutic anticancer drugs include camptothecin, etoposide, vincristine, and paclitaxel.These drugs have been use in cancer treatment for many years. Polydatin (PD) is one ofthe main effective elements of Polygonum cuspidatum. Pharmacological studies andclinical practice have demonstrated that polydatin has many biological functions, suchas protective effect against shock ischemia/reperfusion injury, congestive heart failure,and endometriosis. However, the effects of polydatin on human cancer cells have rarelybeen reported.In this study, a series of methods, including MTT assay, in vitro wound healingassay, in vitro cellular adhesion assay, and Transewell migration and invasion assay,were employed to determine cell growth and proliferation, invasion and migration. Flowcytometry was used to determine alteration of cell cycle progression and apoptosis.Human phosphor-kinase array, human apoptosis array and western blot assays wereemployed to investigate expression of proteins related to cell growth, cell cycle, andapoptosis. In animal studies, nude mice lung cancer transplant models were used toinvestigate tumor growth.As observed by MTT assay, polydatin has a broad spectrum of growth inhibition effects against10cancer cell lines. It is more potent to kill cancer cells than non-cancercells. It inhibited cell growth in a dose-and tome-dependent fashion. Animal studiesalso showed polydatin could inhibit tumor growth and did not have significant sideeffects. Flow cytometry assay indicated polydatin induced apoptosis and cell cycle Sphase arrest in breast and lung cancer cells. Human phosphor-kinase array, humanapoptosis array and western blot assays indicated the anti-proliferation and cell cyclearrest effects of polydatin might be associated with down regulation of pCREB andcyclinD1. Polydatin induced apoptosis through both intrinsic and extrinsic pathway. Baxis the major target in intrinsic pathway.In breast and lung cancer cells, polydatin significantly decreased the ability of celladhesion, cell migration and invasion at non-toxic dosage. Up-regulation of E-Cadherin,-Catenin and down-regulation of N-Cadherin partly contributed to these effects.Polydatin also showed great potential in inhibiting cell growth of adriamycin-resistantbreast cancer cells through inducing apoptosis and cell cycle G0/G1phase arrest.CyclinD1, Bcl-2, Bax and NF-B are involved in the inhibitory effect of polydatin inadriamycin-resistant breast cancer cells.In conclusion, polydain not only inhibits cancer growth both in vitro and in vivo,but also reduces ability of cell adhesion, migration and invasion. Furthermore, polydatinmay inhibit proliferation of drug resistant cells. These studies, for the first time,demonstrated that polydatin might be a promising compound for breast and lung cancertreatment. Although the exact mechanisms need to be further investigated, multiplepathways involved in cell cycle progression and apoptosis including pCREB, cyclinD1and Bcl-2family have been identified in the this study.