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

Indian Journal of Pharmaceutical Education and Research

  • Sumathi Raguraman1Department of Biochemistry, Rabiammal Ahamed Maideen College for Women, Tiruvarur, Tamil Nadu, INDIA.
  • Hesham S Almoallim2Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, SAUDI ARABIA.
  • Tahani Awad Alahmadi3Department of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University, Medical City, Riyadh, SAUDI ARABIA.
  • Samer Hasan Hussein-Al-Ali4Department of Chemistry, Faculty of Science, Isra University, Amman, JORDAN.
  • Muruganantham Bharathi5Department of Biochemistry, Centre for Bioinformatics, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, INDIA.
  • Arun Kumar Ramu6Centre for Applied Research, Institute of Biotechnology, Saveetha School of Engineering (SSE), Saveetha Institute of Technical and Medical Sciences (SIMATS), Saveetha University, Thandalam, Chennai, Tamil Nadu, INDIA.

Volume 58 Issue 3s Pages s900-s909

DOI: 10.5530/ijper.58.3s.91

Abstract

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.

Keywords

  • Reserpine
  • STAT3
  • NF-κB
  • ROS
  • Apoptosis
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