The natural terthiophene α-terthienylmethanol induces S phase cell cycle arrest of human ovarian cancer cells via the generation of ROS stress.

Ovarian cancer is the most lethal gynecological malignancy worldwide. Thiophenes such as terthiophene have been shown to have anti-tumor effects on several cancer cell lines, including ovarian cancer cells. However, the underlying mechanisms behind the anti-proliferative effect of thiophenes are poorly understood. In this study, we investigated the molecular mechanisms underlying the anti-proliferative effect of α-terthienylmethanol, a terthiophene isolated from Eclipta prostrata (False Daisy), on human ovarian cancer cells. We found that α-terthienylmethanol is a more potent inhibitor of cell growth than is cisplatin in human ovarian cancer cells. α-Terthienylmethanol induces cell cycle arrest in ovarian cancer cells, as shown by the accumulation of cells in S phase. In addition, α-terthienylmethanol induced a change in S phase-related proteins cyclin A, cyclin-dependent kinase 2, and cyclin D2. Knockdown of cyclin A using specific siRNAs significantly compromised α-terthienylmethanol-induced S phase arrest. We further demonstrated that α-terthienylmethanol induced an increase in intracellular ROS, and the antioxidant N-acetyl-l-cysteine significantly reversed the S phase arrest induced by α-terthienylmethanol. Moreover, α-terthienylmethanol significantly increased the levels of p-H2AX, a DNA damage marker. These results suggest that α-terthienylmethanol inhibits the growth of human ovarian cancer cells by S phase cell cycle arrest via induction of ROS stress and DNA damage.