Generation of reactive oxygen species by polyenylpyrroles derivatives causes DNA damage leading to G2/M arrest and apoptosis in human oral squamous cell carcinoma cells.

摘要: Oral squamous cell carcinoma (OSCC) accounts for 5.8% of all malignancies in Taiwan and the incidence OSCC is on rise. also a common malignancy worldwide five-year survival rate remains poor. Therefore, new effective treatments are needed to control OSCC. In present study we have investigated efficacy associated mechanisms polyenylpyrroles their analogs both vitro culture vivo nude mice xenografts. Auxarconjugatin B (compound 1a) resulted cycle arrest G2/M phase caspase-dependent apoptosis OEC-M1 HSC-3 cells by activating DNA damage mitochondria dysfunction through loss mitochondrial membrane potential, release cytochrome c, increase B-cell lymphoma-2-associated X protein level, decrease lymphoma-2 level. Compound 1a-induced generation intracellular reactive oxygen species P450 1A1 was identified as major mechanism its effect damage, apoptosis, which reversed antioxidant N-acetylcysteine well inhibitor specific siRNA. Furthermore, compound 1a-treated showed reduction xenograft tumor growth an caspase-3 activation tissue. These results provide promising insights how 1a mediates cytotoxicity may prove be molecular rationale translation into potential therapeutic against