Reserpine Induces Apoptosis in Drug-Resistant Cancer through Modulating STAT3 and NF-κB Signaling

Introduction

A major feature of drug-resistant cancer is the overexpression of transcription factors. During the study, reserpine, an indole alkaloid, was examined for its anticancer effects on cancer with drug resistance.

Objectives

The objective of this study was to explore the anti-apoptotic impacts of reserpine in drug-resistant cancer cells by impeding the nuclear translocation of NF-κB and STAT3.

Materials and Methods

For the in vitro study of reserpine’s anticancer activity, human drug resistance cancer cell line KB-ChR-8-5 was selected. A MTT assay was used to evaluate the cytotoxicity of reserpine. Reactive Oxygen Species (ROS), comet test, Mitochondrial Membrane Potential (MMP) and AO/EtBr staining were used to assess cell proliferation, DNA damage and apoptotic activation. Conducting western blot analysis was employed in this research study to examine the effect of reserpine on KB-ChR-8-5 cells express levels of proteins related to apoptosis markers and transcription factor expression.

Results

We found that, reserpine decreased cell viability, increased ROS levels, enhanced DNA damage and decreased mitochondrial membrane potential due to its antioxidant properties. Moreover, the suppression of NF-κB and STAT3 facilitates the upregulation of specific apoptotic proteins, such as Bax, cytochrome C, Caspase-9 and Caspase-3, which simultaneously inhibit cancer growth.

Conclusion

These results imply that reserpine suppressed NF-κB and STAT3 nuclear translocation process, which led to ROS-induced apoptosis and tumour cell death.