Bafilomycin A1 inhibits autophagy and induces apoptosis in MG63 osteosarcoma cells

Mol Med Rep. 2014 Aug;10(2):1103-7. doi: 10.3892/mmr.2014.2281. Epub 2014 May 29.

Abstract

The purpose of the present study was to investigate the effects of bafilomycin A1 (BafA1) on proliferation, apoptosis and autophagy in MG63 osteosarcoma cells. The growth rate of MG63 cells was determined using a Cell Counting Kit‑8 assay. The mitochondrial membrane potential (Δψ) was measured using a fluorescent probe, JC‑1, and the inhibition of autophagy and apoptosis was monitored by transmission electron microscopy. In addition, the inhibition of autophagy was monitored by western blot analysis of microtubule‑associated protein 1 light chain 3 (LC3), and the ratio of LC3‑II/LC3‑I protein levels was calculated as an indicator of the extent of autophagy. Furthermore, the expression levels of specific proteins associated with autophagy, including p53, Beclin1 and p62, were detected in cultured MG63 cells by western blotting. It was shown that the viability of MG63 cells was inhibited following the use of BafA1, and an induction in the expression levels of the apoptosis‑related protein p53 and the autophagic protein Beclin1 was detected. Furthermore, a collapse in Δψ was observed, together with an induction of apoptotic cell death, following treatment with BafA1. Therefore, following BafA1‑mediated inhibition of autophagy, the inhibition of MG63 cell proliferation and induction of apoptosis were observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Humans
  • Lysosomes / metabolism
  • Macrolides / toxicity*
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA-Binding Proteins / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • MAP1LC3A protein, human
  • Macrolides
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • P62 protein, human
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • bafilomycin A1