A Novel Approach to Unraveling the Apoptotic Potential of Rutin (Bioflavonoid) via Targeting Jab1 in Cervical Cancer Cells

Abstract

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

Rutin Potentially Binds the Gamma Secretase Catalytic Site, Down Regulates the Notch Signaling Pathway and Reduces Sphere Formation in Colonospheres

“…Studies conducted by other investigators revealed that rutin lowers the expression of Hes-1 and Notch-1 genes in cervical cancer cells [ 18 ]. Furthermore, rutin also induced apoptosis of cervical cancer cells by interacting with Jab1 [ 17 ]. It has been reported that notch signaling is involved in the regulation of cell-to-cell connection and cell motility which are important for the EMT of cancer cells.…”

“…Rutin has recently been demonstrated to regulate Notch-1 and Hes-1 mRNA levels in cervical cancer cells. Furthermore, rutin has been demonstrated to have modulated the signaling pathways in cancer cells and cause apoptosis [ 16 , 17 ]. In a recently published study, rutin was found to cause apoptosis of cervical cancer cells by downregulation of the Notch-1 and Hes-1 genes [ 18 ].…”

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

“…The enzymatic activities of six pyrazole-based Schiff bases, 5a, 5d, 5e, 5f, 7a, and 7f, against caspase-3 and Bcl-2 were evaluated according to the reported techniques in the literature [87,88].…”

Screen natural terpenoids to identify potential Jab1 inhibitors for treating breast cancer

“…Since Jab1 is an EGFR signaling target in both ER-cell lines and breast tumors, it may serve as a common factor and possible therapeutic target for crucial cell signaling pathways in ER breast cancer [21][22][23] . Elucidation of new medicinal phytochemicals targeting Jab1 signalosome provides a new path toward finding a better cancer therapeutic approach [24][25][26][27][28][29] . Jab1 has also been involved in breast cancer progression.…”