The mechanism of anticancer activity of the new synthesized compound - 6,7-Methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin??2(1 H)-one(12e) in human ovarian cancer cell lines

摘要

ObjectiveOvarian cancer is the most lethal of the gynecologic malignancies. Most women have advanced disease at diagnosis and require extensive debulking surgery and aggressive chemotherapy. Induction of apoptosis in cancer cells has been used as an important approach for cancer therapy. We examined the anticancer effect of 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) in human ovarian cancer cell line.Materials and methodsThe 6,7-methylenedioxy-4- (2,4-dimethoxyphenyl) quinolin-2 (1H) -one (12e) was synthesized and provided by Dr. Li-Jiau Huang of China Medical University. Cell viability analysis showed that12einhibited cell growth and induced cell death in time- and dose-dependent manners. In order to study the underlying cell death mechanism, 2774 and SKOV3 cells treated with12ewere studied by morphology, DAPI/TUNEL double staining, DNA gel electrophoresis. To search the mechanisms of anti-proliferative effect of12e, cell cycle analysis was performed. Changes in proteins related to cell death were analyzed by Western blot.Results12e significantly induced apoptosis evidenced by morphological changes, TUNEL-DAPI double-staining and DNA fragmentation. Western blot analysis demonstrated that the protein level of Bcl-2 was decreased after treatment with12e, while the level of p53 and Bax was increased.12etreatment resulted in G2/M arrest through down modulation of cyclin B1 and cdk1.ConclusionThese results suggested that12e-induced growth inhibition was associated with cell cycle arrest and apoptosis.