A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Biomed Res Int. 2020 Aug 25:2020:4929053. doi: 10.1155/2020/4929053. eCollection 2020.

Abstract

Background: Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism.

Methods: Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot.

Results: Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis.

Conclusion: Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Imidazoles / chemistry
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Pyridines / chemistry
  • Time Factors

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Pyridines
  • imidazopyridine