SMBA1, a Bax Activator, Induces Cell Cycle Arrest and Apoptosis in Malignant Glioma Cells

Pharmacology. 2020;105(3-4):164-172. doi: 10.1159/000500292. Epub 2019 Dec 19.

Abstract

SMBA1 (small-molecule Bax agonists 1), a small molecular activator of Bax, is a potential anti-tumour agent. In the present study, we investigated the biological effects of SMBA1 on glioblastoma (GBM) cells. SMBA1 reduced the viabilities of U87MG, U251 and T98G cells in a time- and dose-dependent manner. Moreover, treatment with SMBA1 induced cell cycle arrest at the G2/M phase transition, accompanied by the downregulation of Cdc25c and cyclin B1 and the upregulation of p21. SMBA1 also induced apoptosis of GBM cells in a dose-dependent manner. Mechanistically, SMBA1 induced apoptosis via the intrinsic pathway. Silencing of Bax or ectopic expression of Bcl-2 significantly inhibited SMBA1-induced apoptosis. Moreover, SMBA1 inhibited the growth of U87MG xenograft tumours in vivo. Overall, SMBA1 shows anti-proliferative effects against GBM cells through activation of the intrinsic apoptosis pathway.

Keywords: Apoptosis; Bax; Cell cycle arrest; Glioma; SMBA1.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Time Factors
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • bcl-2-Associated X Protein