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

Pratibha Pandey,Mohammad Oves,Faisal Abdulrahman Alzahrani,Huda A Qari,Fahad Khan

doi:10.3390/molecules26185529

Pratibha Pandey, Mohammad Oves + Show 3 more

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https://doi.org/10.3390/molecules26185529

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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.

Highlights

Cancer of the cervix has been recognized as one of the most frequently detected cancers worldwide, and several studies are in the pipeline for elucidating efficient therapeutic approaches against this malignancy [1,2]
The correlation between rutin and Jab1 mRNA expression was assessed by RT-PCR analysis and the associated events with this downregulation were 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
SiHa cells in comparison to that in untreated control cells. These results further suggested that mitochondrial-mediated apoptosis induction could be one of the possible mechanisms behind the growth inhibitory effect of rutin in cervical cancer SiHa cells

Summary

Introduction

Cancer of the cervix has been recognized as one of the most frequently detected cancers worldwide, and several studies are in the pipeline for elucidating efficient therapeutic approaches against this malignancy [1,2]. Inhibition of cervical cancer progression with phytochemicals via modulating numerous signaling pathways has been validated by various published studies [3,4]. Phytochemicals (plant-based products) have received wider significance in exploring potent therapeutic approaches against numerous carcinomas with enormous health benefits [5]. Toxicity associated with several chemotherapeutic approaches has raised the need for the elucidation of better anticancer drugs [6]. Several studies have reported the efficacy of natural phytocompounds as an alternative to surgery and chemotherapeutic drugs. Various natural compounds, including carvacrol, rutin, paclitaxel, vincristine, hesperidin, etoposide, and vinblastine, have shown better medicinal benefits and have been utilized clinically [7]

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