Portal de Periódicos da CAPES

Fisetin inhibits growth, induces G 2 / M arrest and apoptosis of human epidermoid carcinoma A 431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation

2013; Wiley; Volume: 22; Issue: 7 Linguagem: Inglês

10.1111/exd.12181

1600-0625

Harish C. Pal, Samriti Sharma, Craig A. Elmets, Mohammad Athar, Farrukh Afaq,

Bioactive Natural Diterpenoids Research

Abstract Non‐melanoma skin cancers ( NMSC s), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non‐toxic phytochemicals for prevention/treatment of NMSC s is highly desirable. Fisetin (3,3′,4′,7‐tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti‐oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A 431 cells. Treatment of A 431 cells with fisetin (5–80 μ m ) resulted in a significant decrease in cell viability in a dose‐ and time‐dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A 431 cells. Fisetin treatment of A 431 cells resulted in G 2 / M arrest and induction of apoptosis. Furthermore, treatment of A 431 cells with fisetin resulted in (i) decreased expression of anti‐apoptotic proteins ( B cl2; B cl‐xL and M cl‐1); (ii) increased expression of pro‐apoptotic proteins ( B ax, B ak and B ad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and S mac/ DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly( ADP ‐ribose) polymerase ( PARP ) protein. Pretreatment of A 431 cells with the pan‐caspase inhibitor ( Z‐VAD‐FMK ) blocked fisetin‐induced cleavage of caspases and PARP . Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A 431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSC s.