Cimicifugic acid B, a hydroxycinnamic acid ester of Cimicifuga sp., exhibits strong antiproliferative and cytotoxic potential against cervical cancer cells
Recently, many compounds of Cimicifuga sp. have been shown to exhibit antioxidant, anti-inflammatory, antineoplastic, anti-climacteric, antiviral, anti-tumor, and estrogenic properties. Some important phenylpropanoids identified from Cimicifuga sp. like cimicifugic acids and fukinolic acids have been shown to exhibit important biological activities like anti-inflammatory, anti-collagenase, antioxidant, antiviral, and anti-hyaluronidase activity in recent studies. Among these, cimicifugic acid B was found most active in terms of its cytotoxic and antiproliferative property. However, no individual study has been done regarding the anticancer potential of cimicifugic acid B till date. Owing to the traditional medicinal use of Cimicifuga rhizome in gynaecological problems of women, the aim of this study was to explore and delineate the potential of cimicifugic acid B against cervical cancer. Our findings demonstrated that cimicifugic acid B treatment drastically decreased the survival of HPV negative cervical cancer C33A cells evident by a dose-dependent increase in nuclear condensation and DNA fragmentation. Cimicifugic acid B triggered ROS generation in a dose-dependent manner and also caused mitochondrial depolarization, which led to apoptosis. Moreover, Cimicifugic acid B was found to alter Bax/Bcl2 ratio, induce cell cycle arrest in G0/G1 phase, modulate the expression of cell cycle regulatory proteins along with downregulation of Hedgehog pathway. As a result, our results showed the effectiveness of Cimicifugic acid B against cervical cancer cells, suggesting its potential as an adjuvant in the management of cervical cancer along with the current therapeutic regimen.