A NATURAL COUMESTAN WEDELOLACTONE TARGETS INFLAMMATORY CYTOKINES TO INITIATE APOPTOSIS IN HUMAN CERVICAL CANCER CELLSAbstract
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.
R. G. J. Christobel, S. S. Jaganathan, M. P. Abirami, P. Rasappan and S. Shila *
Department of Biochemistry, VRR Institute of Biomedical Science (Affiliated to University of Madras), Chennai, Tamil Nadu, India.
25 August 2019
26 November 2019
29 November 2019
01 December 2019