Abstract

Natural products are being extensively explored for their potential to prevent as well as treat cancer due to their ability to target multiple molecular pathways. Ficus religiosa has been shown to exert diverse biological activities including apoptosis in breast cancer cell lines. In the present study, we report the anti-neoplastic potential of aqueous extract of F. religiosa (FRaq) bark in human cervical cancer cell lines, SiHa and HeLa. FRaq altered the growth kinetics of SiHa (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner. It blocked the cell cycle progression at G1/S phase in SiHa that was characterized by an increase in the expression of p53, p21 and pRb proteins with a simultaneous decrease in the expression of phospho Rb (ppRb) protein. On the other hand, in HeLa, FRaq induced apoptosis through an increase in intracellular Ca2+ leading to loss of mitochondrial membrane potential, release of cytochrome-c and increase in the expression of caspase-3. Moreover, FRaq reduced the migration as well as invasion capability of both the cervical cancer cell lines accompanied with downregulation of MMP-2 and Her-2 expression. Interestingly, FRaq reduced the expression of viral oncoproteins E6 and E7 in both the cervical cancer cell lines. All these data suggest that F. religiosa could be explored for its chemopreventive potential in cervical cancer.

Highlights

  • Cervical cancer is the second major cause of cancer death in the women all over the world [1], [2]

  • We have investigated the putative molecular mechanism underlying the antineoplastic potential of the aqueous extract of F. religiosa (FRaq) bark in cervical cancer

  • We have previously reported that F. religiosa exhibited significant antioxidant potential as well as cytotoxicity in cervical cancer cell lines, HeLa and SiHa [22]

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Summary

Introduction

Cervical cancer is the second major cause of cancer death in the women all over the world [1], [2]. E6 promotes p53 degradation through a ubiquitin-dependent proteasome pathway while E7 associates with retinoblastoma (pRb) protein and interferes with its binding to E2F [4], [5]. This results into loss of Rb/E2F complexes leading to release of transcription factor E2F that induces the expression of cell proliferative genes [5]. More than 60% of currently used anti-cancer drugs are originally derived from natural sources such as plants, marine organisms and microorganisms [9]. Various scientific studies, including ours, have suggested the potential of medicinal plants as anti-cancer drug candidates [10], [11]. We have recently reported the anticancer potential of Cinnamomum cassia (cinnamon) in cervical cancer [12]

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