A novel approach of unraveling the apoptotic potential of carvacrol via targeting Jab1 in cervical cancer cells

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Abstract

  Carvacrol has been well recognized for possessing numerous pharmacological and biological activities in several human cancer cells. This research has addressed the inhibitory potential of carvacrol against Jab1 oncogene in SiHa cancer cells, which is known to inactivate various tumor sup-pressor proteins including p53 and p27. Further, the inhibitory efficacy of carvacrol via Jab1 expres-sion modulation in cervical cancer has not been elucidated yet. Hence, we hypothesized that ru-tin could exhibit strong inhibitory efficacy against Jab1 and thereby induce significant growth arrest in SiHa cancer cell in a dose dependent manner. In our study, the cytotoxic efficacy of carvacrol on the proliferation of cervical cancer cell line (SiHa) was exhibited using MTT and LDH assay. The correlation between carvacrol and Jab1 mRNA expression was assessed by RT-PCR analysis and the associated events (a mechanism) with this downregulation was then explored via perform-ing ROS assay, DAPI analysis, and expression analysis of apoptosis-associated signaling mole-cules such as Bax, Bcl-2, Caspase-3, and -9 using qRT-PCR analysis. Results exhibit that carvacrol produces anticancer effects via inducing modulation in the expression of oncogene as well as tumor suppressor gene. Further apoptotic induction, caspase activation, and ROS generation in carvacrol-treated SiHa cancer cells explain the cascade of events associated with Jab1 downregulation in SiHa cancer cells. Additionally, apoptosis induction was further confirmed by FITC-Annexin V/PI double staining method. Altogether, our research supports the feasibility of developing ru-tin as one of the potent drug candidates in cervical cancer management via targeting one such crucial oncogene associated with cervical cancer progression.

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