Oleanolic acid conjugated chitosan nanocomplex exerts anti-tumor effects by inhibiting autophagy in lung cancer cells through the signal transducers and activators of transcription 3/B cell lymphoma-2 signaling pathway

J Physiol Pharmacol. 2024 Jun;75(3). doi: 10.26402/jpp.2024.3.08. Epub 2024 Jul 18.

Abstract

The current study reveals the anticancer potential of oleanolic acid conjugated chitosan nanocomplex (OAC) in lung cancer (LC). Cell counting kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay were used to detect cell viability, 5-ethynyl-2'-deoxyuridine (EdU) assay to detect cell proliferation, flow cytometry and TUNEL assay to detect cell apoptosis in A549 (ATCC®CCL-185™) and NCIH460 cells. Transwell evaluated cell migration and invasion ability, transmission electron microscopy and immunofluorescence observed autophagy, and Western blotting detected apoptosis- and autophagy-associated proteins. OAC inhibited LC cell viability, migration, and invasion, and induced apoptosis and autophagy depending on the concentration. The phosphorylation of signal transducers and activators of transcription 3 (STAT3) in cells was weakened after OAC treatment. STAT3 activation restored the inhibition of cell viability and induction of apoptosis by OAC. We conclude that OAC induces apoptosis and inhibits cell viability, which may be related to the STAT inactivation. Therefore, OAC is a promising compound for LC therapy.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents* / pharmacology
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Oleanolic Acid* / analogs & derivatives
  • Oleanolic Acid* / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction* / drug effects

Substances

  • STAT3 Transcription Factor
  • Oleanolic Acid
  • Chitosan
  • STAT3 protein, human
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • BCL2 protein, human