| dc.description.abstract | Green tea epigallocatechin gallate (EGCG) and betel nut arecoline have been reported to regulate blood testosterone level and prostate gland growth in rats, respectively. However, a clear interaction between EGCG and arecoline on human prostate cancer cells was not reported. Using androgen-independent human PC-3 prostate cancer cells, we found that EGCG had a synergistic effect with arecoline to reduce the cell viability. When growth signaling molecules were examined, the combination of arecoline and EGCG treatment significantly reduced the level of cylin-dependent kinase (CDK) 1, CDK4 and CDK6, but not CDK2, relative to the arecoline group or the control. Interestingly, when the endogenous CDK activators cyclins were examined, EGCG antagonized the arecoline-induced increase in cyclin B1 protein, and EGCG in combination with arecoline significantly lowered the levels of cyclins D1 and D3 compared with the arecoline group. When the endogenous CDK inhibitors (CKIs) were examined, EGCG further reduced arecoline-suppressed p21 protein level but both EGCG and arecoline had no effect on the p18 protein expression. Moreover, EGCG enhanced the arecoline-increased PARP apoptotic protein level as well as the LC3β-II but not LC3β-I autophagic protein levels. Interestingly, EGCG and the antioxidant N-acetylcysteine (NAC) were found to prevent arecoline-induced reactive oxygen species (ROS) production. However, NAC enabled to reverse the suppressive effect of arecoline, and the combination of arecoline and EGCG on cell viability, while it did not alter EGCG-induced decrease in cell viability. These results suggest that the mechanisms for the combinatorial effect of EGCG with arecoline on PC-3 cell growth may be related to certain pathways, such as the modulations of particular CDK, cyclin, and CKI family members, processes of autophagy and apoptosis, and the redox status. | en_US |