INVOLVEMENT OF REACTIVE OXYGEN SPECIES IN GOSSYPOL-INDUCED INHIBITORY EFFECTS ON HUMAN PROSTATE CANCER CELLS

التفاصيل البيبلوغرافية
العنوان: INVOLVEMENT OF REACTIVE OXYGEN SPECIES IN GOSSYPOL-INDUCED INHIBITORY EFFECTS ON HUMAN PROSTATE CANCER CELLS
المؤلفون: Yu, Ching-Han, Chen, Pei-Chi, Wang, Paulus
المصدر: Biology of Reproduction; July 2007, Vol. 77 Issue: 1, Number 1 Supplement 1 p214-214, 1p
مستخلص: Gossypol, a natural polyphenol extracted from the cottonseeds, is conventionally used as a male contraceptive drug, and displays the prooxidant capability. Previous studies have indicated that gossypol exhibits the antiproliferative and antimetastasis effects in various cancers through the mechanisms including influencing the cell cycle regulators, elevating the secretion of transforming growth factor beta-1 (TGF beta-1), and modulating the apoptosis-related molecules. However, there are few investigations about the relation of the pro-oxidant capacity and the antitumor activity of gossypol. In the present study, the role of reactive oxygen species (ROS) induced by gossypol and its analog, acetic acid gossypol, was evaluated on the malignantly androgen-independent prostate cancer cell lines, PC3 and DU145. Base on the results of the MTT assay and the trypan blue exclusion assay, the cell proliferation and cell numbers were down-regulated by gossypol and acetic acid gossypol at the concentration of 10 to 20 microM after the treatment from 2 to 4 days in both cell lines. In addition, gossypol and acetic acid gossypol also caused the cleavage of PARP and the process of procaspase 7. Results from the flow cytometer showed that gossypol and acetic acid gossypol stimulated the production of ROS, including superoxide, nitric oxide and hydrogen peroxide in PC3 and DU145 cells. Superoxide was elevated at 6 hours after treatment, but nitric oxide and hydrogen peroxide were increased at 18 hours following the administration of gossypol and acetic acid gossypol. According to the data of morphological observation, after the treatment of the combinations of the general antioxidant, vitamine E, or ROS scavengers, superoxide dismutase and catalase, with gossypol or acetic acid gossypol, the phenomena of cell membrane shrinkage and cell rounded up induced by gossypol or acetic acid gossypol treatment alone are partially reversed. Besides, the cleavage of PARP and the process of caspase 7 caused by gossypol were also reversed after the combination treatment. These results suggested that ROS might be involved in the gossypol- and acetic acid gossypol-induced antitumor effects on human prostate cancer cells, and would provide more information about the mechanism of gossypol on the treatment of cancer. (platform)
قاعدة البيانات: Supplemental Index
الوصف
تدمد:00063363
15297268
DOI:10.1093/biolreprod/77.s1.214