Effect of Resveratrol Treatment on Human Pancreatic Cancer Cells through Alterations of Bcl-2 Family Members

Abstract

Pancreatic cancers are among of the most lethal types of neoplasms, and are mostly detected at an advanced stage. Conventional treatment methods such as chemotherapy or radiotherapy often do not bring the desired therapeutic effects. For this reason, natural compounds are increasingly being used as adjuvants in cancer therapy. Polyphenolic compounds, including resveratrol, are of particular interest. The aim of this study is to analyze the antiproliferative and pro-apoptotic mechanisms of resveratrol on human pancreatic cells. The study was carried out on three human pancreatic cancer cell lines: EPP85-181P, EPP85-181RNOV (mitoxantrone-resistant cells) and AsPC-1, as well as the normal pancreatic cell line H6c7. The cytotoxicity of resveratrol in the tested cell lines was assessed by the colorimetric method (MTT) and the flow cytometry method. Three selected concentrations of the compound (25, 50 and 100 µM) were tested in the experiments during a 48-h incubation. TUNEL and Comet assays, flow cytometry, immunocytochemistry, confocal microscopy, real-time PCR and Western Blot analyses were used to evaluate the pleiotropic effect of resveratrol. The results indicate that resveratrol is likely to be anticarcinogenic by inhibiting human pancreatic cancer cell proliferation. In addition, it affects the levels of Bcl-2 pro- and anti-apoptotic proteins. However, it should be emphasized that the activity of resveratrol was specific for each of the tested cell lines, and the most statistically significant changes were observed in the mitoxantrone-resistant cells.

Keywords

• resveratrol
• Bax
• Bcl-2
• Caspase-3
• apoptosis
• multidrug resistance