Natural Antioxidant Prenylflavonoids Attenuate UVA-induced Damage in Human Kerationcytes and Fibroblasts, and Enhance Growth Inhibition in Human Prostate Cancer Cells

• Main Authors: Chien-Ming Wu, 吳健明
• Other Authors: Ming-Hong Yen
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/27042706966522283008

碩士 === 高雄醫學大學 === 藥學研究所碩士在職專班 === 100 === ■ ABSTRACT The antioxidant properties of prenylflavonoids, cycloheterophyllin (AH-C) and heterophyllin (AH-H), isolated from Artocarpus heterophyllus Lamk, was evaluated. AH-C and AH-H displayed a strong inhibitory effect on xanthine oxidase (XO) activity with an IC50 values of 29.4 ± 0.6 and 10.9 ± 1.8 μM, respectively, potent 2,2''-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation scavenging activity with an IC50 values of 25.9 ± 0.6 and 44.1 ± 0.9 μM, and significantly 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity with an IC50 values of 16.8 ± 0.9 and 53.6 ± 8.7 μM, respectively. These findings indicate that AH-C and AH-H are promising antioxidants. Exposure of UVA or UVB radiation induced the production of free radicals or inflammation that lead to a wide array of skin disease. AH-C and AH-H, a kind of polyphenols with strong antioxidant, may significantly contribute to its properties. To test this hypothesis, we found that AH-C and AH-H exhibited significant protective effect against UVA irradiation damage on human fibroblasts, Hs68 cell line. The combination of COX-1 and COX-2 inhibitors indicated a highly effective treatment modality for carcinoma of both the bladder and prostate cancers. We found that AH-C, a potent COX-1 inhibitor, significantly inhibited cell proliferation in PC3 cells with a IC50 value of 1.1 ± 1.9 and 1.7 ± 0.5 μM after treating cells for 48 and 72 hours, respectively. Exposure of PC3 to AH-C significantly increased the generation of reactive oxygen species (ROS) in cells. Flow cytometric analysis exhibited that treatment of PC3 with AH-C led to the cell cycle arrest, accompanied by an increase in apoptotic cells death after 72 h. These data suggest that the presentation of S and G2/M phases arrest and apoptosis in AH-C treated PC3 for 72 h mediated through increased amount of ROS in cells exposed to AH-C. These findings indicated that AH-C could be a promising anticancer agent for treatment of prostate cancer.