Oridonin induces the apoptosis of mucoepidermoid carcinoma cell lines in a myeloid cell leukemia‑1‑dependent manner

Int J Oncol. 2020 Jul;57(1):377-385. doi: 10.3892/ijo.2020.5061. Epub 2020 May 7.

Abstract

Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported to exhibit anticancer activities in several tumors. The aim of the present study was to investigate the anticancer effects and molecular mechanisms of oridonin in mucoepidermoid carcinoma (MEC). Treatment with oridonin induced the apoptosis of MC‑3 and YD‑15 cell and inhibited the expression of myeloid cell leukemia‑1 (MCL‑1) through the regulation of the protein level through post‑translational regulation in these cell lines. Oridonin significantly increased the expression level of truncated Bid (t‑Bid) as a downstream target of MCL‑1 and subsequently decreased the mitochondrial membrane potential. The ectopic expression of MCL‑1 protein was sufficient to reverse the induction of apoptosis and the increased t‑Bid expression induced by oridonin in both cell lines. Taken together, these results suggest that oridonin exerts an apoptotic effect through the modulation of MCL‑1 and t‑Bid in human MEC cell lines and may thus be a potential anticancer drug candidate for the treatment of human MEC.

Keywords: mucoepidermoid carcinoma; oridonin; apoptosis; myeloid cell leukemia‑1; truncated‑Bid.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Carcinoma, Mucoepidermoid / metabolism
  • Carcinoma, Mucoepidermoid / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diterpenes, Kaurane / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
  • Protein Processing, Post-Translational / drug effects
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Diterpenes, Kaurane
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • oridonin