Capsaicin induces cytotoxicity in human osteosarcoma MG63 cells through TRPV1-dependent and -independent pathways

Cell Cycle. 2019 Jun;18(12):1379-1392. doi: 10.1080/15384101.2019.1618119. Epub 2019 May 29.

Abstract

An accumulating body of evidence has shown that capsaicin induces apoptosis in various tumor cells as a mechanism of its anti-tumor activity. However, the effects of capsaicin on osteosarcoma have not been studied extensively. In the current study, we explore the molecular mechanism of capsaicin-mediated tumor suppressive function in osteosarcoma. We found that capsaicin-induced apoptosis and the activation of transient receptor potential receptor vanilloid 1 (TRPV1) in a dose- and time-dependent manner in human osteosarcoma MG63 cells in vitro. Blocking TRPV1 using capsazepine attenuated the capsaicin-induced cytotoxicity, mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity. In addition, the results demonstrated that capsaicin induced the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK), p53 and C-jun N-terminal kinase (JNK). In addition, Compound C (antagonist of AMPK) attenuated the activation of p53, which appeared to be TRPV1 independent. Taken together, the present study suggests that capsaicin effectively causes cell death in human osteosarcoma MG63 cells via the activation of TRPV1-dependent (mitochondrial dysfunction, and overproduction of ROS and JNK) and TRPV1-independent (AMPK-p53) pathways. Thus, capsaicin may be a potential anti-osteosarcoma agent.

Keywords: Osteosarcoma; TRPV1; apoptosis; capsaicin; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Apoptosis / drug effects*
  • Capsaicin / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Humans
  • Ion Channel Gating / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects
  • Superoxide Dismutase / metabolism
  • TRPV Cation Channels / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Tumor Suppressor Protein p53
  • Cytochromes c
  • Superoxide Dismutase
  • JNK Mitogen-Activated Protein Kinases
  • Adenylate Kinase
  • Capsaicin

Grants and funding

This work was supported by the Nature Science Major and Key Program of College and University of Anhui Province (No. KJ2018ZD024 and KJ2016A460), Key Projects of Support Program for Outstanding Young Talents in Colleges and Universities of Anhui Province (No. gxyq2017032), and the Nature Science Foundation of Bengbu Medical University (No.BYKF1771 and No. BYKF1708ZD).