In the present study, we evaluated 3-Hydroxyter-phenyllin (3-HT) as a potential anticancer agent using the human ovarian cancer cells A2780/CP70 and OVCAR-3, and normal human epithelial ovarian cells IOSE-364 as an in vitro model. 3-HT suppressed proliferation and caused cytotoxicity against A2780/CP70 and OVCAR-3 cells, while it exhibited lower cytotoxicity in IOSE-364 cells. Subsequently, we found that 3-HT induced S phase arrest and apoptosis in a dose-independent manner. Further investigation revealed that S phase arrest was related with DNA damage which mediated the ATM/p53/Chk2 pathway. Downregulation of cyclin D1, cyclin A2, cyclin E1, CDK2, CDK4 and Cdc25C, and the upregulation of Cdc25A and cyclin B1 led to the accumulation of cells in S phase. The apoptotic effect was confirmed by Hoechst 33342 staining, depolarization of mitochondrial membrane potential and activation of cleaved caspase-3 and PARP1. Additional results revealed both intrinsic and extrinsic apoptotic pathways were involved. The intrinsic apoptotic pathway was activated through decreasing the protein levels of Bcl2, Bcl-xL and procaspase-9 and increasing the protein level of Puma. The induction of DR5 and DR4 indicated that the extrinsic apoptotic pathway was also activated. Induction of ROS and activation of ERK were observed in ovarian cancer cells. We therefore concluded that 3-HT possessed anti-proliferative effect on A2780/CP70 and OVCAR-3 cells, induced S phase arrest and caused apoptosis. Taken together, we propose that 3-HT shows promise as a therapeutic candidate for treating ovarian cancer.

Bacterial infection stimulates nitric oxide (NO) production in chondrocytes. However, the role of NO in chondrocyte apoptosis after infection remains unclear. The purpose of the study was to test if inhibition of NO could ameliorate apoptosis and modulate matrix protein gene expression in bacteria-infected chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM) significantly decreased the release of NO (from 72 to 14 pM) and the extent of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted the bacteria-induced downregulation of Type I1 collagen (from 26% to 79%) and aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of infection could not decrease the extent of apoptosis and modulate matrix protein gene expression. The results of this study support the hypothesis that NO has an important role in bacteriainduced chondrocyte apoptosis. Pre-treatment but not post-treatment could ameliorate the extent of apoptosis and reestablish the cartilage matrix protein gene expression. This study suggests that in addition to NO, other mechanisms may be responsible for the sustained destruction of articular cartilage in the post-infectious arthropathy.