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Apoptosis is a regulated process of programed cell death that removes damaged ells. GO-Y078, a new curcumin analog, has been studied in the oncology field and shown to exert anti-proliferative and anti-angiogenic effects in multiple tumor types. However, its detailed signaling mechanisms and functional effects in human cervical cancer have not been clarified. Herein, GO-Y078 was employed to examine the anti-cancer mechanism in cervical cancer cells. GO-Y078 reduced the cell viability and elicited chromatin condensation and apoptotic cells of human cervical SiHa and HeLa cancer cells. Active PARP and active caspase-9, -8, and -3 were involved in GO-Y078-stimulated apoptosis. GO-Y078 also elevated phosphorylation of mitogen-activated protein kinase (MAPK) pathway. Co-treatment with GO-Y078 and either the ERK inhibitor U0126 or the p38 inhibitor SB203580 significantly reduced GO-Y078-induced activation of caspase-9, -8, and -3. In conclusion, GO-Y078 is a potential therapeutic candidate that induces apoptotic cell death in cervical cancer cells through phosphorylation-dependent activation of MAPK signaling followed by caspase activation.