Oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling

Int J Clin Exp Pathol. 2015 Nov 1;8(11):13864-70. eCollection 2015.

Abstract

Oleanolic acid has significant pharmacological activities, such as anti-tumor, regulating blood sugar level and liver protection, which are more effective compared with free aglyconeoleanolic acid. However, it is still unknown if oleanolic acid affects the proliferation of human bladder cancer. We utilized T24 cells to study the effect of oleanolic acid on the proliferation and apoptosis of human bladder cancer. In this study, we found that the anti-cancer effect of oleanolic acid significantly suppressed cell proliferation and increased apoptosis and caspase-3 activity of T24 cells. Furthermore, Akt, mTOR and S6K protein expression was greatly inhibited in T24 cells under oleanolic acid treatment. Meanwhile, ERK1/2 of phosphorylation protein expression was significantly promoted by oleanolic acid treatment. Taken together, we provided evidences that oleanolic acid was Akt/mTOR/S6K and ERK1/2 signaling-targeting anti-tumor agent. These findings represent new evidences that oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling, and oleanolic acid may be used to prevent human bladder cancer.

Keywords: Akt; ERK1/2; Oleanolic acid; S6K; bladder cancer; mTOR.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Oleanolic Acid / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Ribosomal Protein S6 Kinases / metabolism*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Oleanolic Acid
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • CASP3 protein, human
  • Caspase 3