A NATURAL COUMESTAN WEDELOLACTONE TARGETS INFLAMMATORY CYTOKINES TO INITIATE APOPTOSIS IN HUMAN CERVICAL CANCER CELLS

Objective: Wedelolactone is a naturally (WDL) occurring coumestan of phytoestrogen category that possess anticancer and anti-inflammatory property. In this study, the anti-inflammatory effect of WDL on human cervical cancer cells (HeLa) and initiation of apoptosis mechanism were investigated. Methods: MTT assay and Trypan blue assay were demonstrated to detect the inhibitory effects of WDL on cell proliferation. The mRNA expression of IL-1β, TNFα, IL-6, TGFβ, and NFκB were detected by RT PCR. Western blotting was performed to detect the expression of apoptosis-associated proteins; cleaved caspase-3, cleaved PARP, Bcl-2, and Bax. Results: WDL significantly inhibited the growth and proliferation of HeLa cells in a concentration dependent manner with the IC₅₀ of 10µM. mRNA expression of inflammatory cytokines and NFκB was significantly reduced in WDL treated groups. Moreover, WDL promoted the apoptosis of HeLa cells dose-dependently by down-regulating Bcl-2 and up-regulating cleaved caspase-3, cleaved PARP, and Bax. Conclusion: Collectively, WDL exerted anti-inflammatory effect through the suppression of NF-kB activation, IL-1β, TNFα, IL-6 and promoted apoptosis in HeLa cells. Thus, use of WDL, especially through its anti-inflammatory effect, may have future applications in treating human cancers by sensitizing cancer cells to conventional cancer therapies.