The Aqueous Extract of Ficus religiosa Induces Cell Cycle Arrest in Human Cervical Cancer Cell Lines SiHa (HPV-16 Positive) and Apoptosis in HeLa (HPV-18 Positive)

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.

Ficus extract—A promising agent for antimammary tumorigenesis: A review on current status and future possibilities

“…Reports suggest that phenolic compounds present in Ficus extract possess the ability to inhibit angiogenesis through the down regulation of basic fibroblast growth factor/VEGF (Fotsis et al, ) eventually impeding tumor progression. They are understood to target the activity of matrix metalloproteinases‐2 (MMP‐2) thereby reducing HER‐2 expression (Choudhari, Suryavanshi, & Kaul‐Ghanekar, ) and ceasing migration and inversion. In concurrence with this, O'leary et al () observed downregulation of cyclooxygenase‐2 (COX‐2) and lipooxygenase‐5 enzymes.…”

“…• Induces cell cycle arrest by blocking the cell cycle progression at G1/S phase (Choudhari et al, ).…”

Pharmacology of Ficus religiosa- A review

“…The aqueous extract of Ficus religiosa also reduced the migration as well as invasion capability of both cervical cancer cell lines accompanied with down-regulation of MMP-2 and Her-2 expression. In addition, it also reduced the expression of viral oncoproteins E6 and E7 in both cervical cancer cell lines [106]. Different fractions of Ficus religiosa [FR] were tested for in vitro anticancer activity using human MCF 7 and normal epithelial cell lines.…”

Bothrops jararacaandBothrops erythromelasSnake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

“…In Brazil, it is estimated that there are 16,340 new cases of cervical cancer in 2016 [5]. High-risk human papilloma viruses (HPVs) such as HPVs 16, 18, 31, and 33 have been attributed to being the major risk factors for cervical cancer, out of which HPVs 16 and 18 account for almost 70% of the cancers [6, 7]. …”