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

•α-Terthienylmethanol is a terthiophene isolated from a perennial herb Eclipta prostrata.•We examined the growth inhibitory effects of α-terthienylmethanol in human ovarian cancer cell.•α-Terthienylmethanol induces S phase cell cycle arrest by regulating S phase-related proteins.•α-Terthienylmethanol also induces DNA damages in ovarian cancer cells.•ROS stress is associated with α-terthienylmethanol-induced cell cycle arrest.

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.

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