The critical role of quercetin in autophagy and apoptosis in HeLa cells

Tumour Biol. 2016 Jan;37(1):925-9. doi: 10.1007/s13277-015-3890-4. Epub 2015 Aug 11.

Abstract

In recent years, the effects of quercetin on autophagy and apoptosis of cancer cells have been widely reported, while effects on HeLa cells are still unclear. Here, HeLa cells were subjected to quercetin treatment, and then proliferation, apoptosis, and autophagy were evaluated using MTT, flow cytometry, and MDC staining, respectively. The LC3-I/II, Beclin 1, active caspase-3, and S6K1 phosphorylation were detected using Western blot assay. The ultrastructure of HeLa was observed via transmission electron microscope (TEM). Our findings showed that quercetin can dose-dependently inhibit the growth of HeLa cells. The MDC fluorescence was enhanced with increased concentration of quercetin and hit a plateau at 50 μmol/l. Western blot assay revealed that LC3-I/II ratio, Beclin 1, and active caspase-3 protein were enforced in a dose-dependent method. However, the phosphorylation of S6K1 gradually decreased, concomitant with an increase of autophagy. In addition, TEM revealed that the number of autophagic vacuoles was peaked at 50 μmol/l of quercetin. Besides, interference of autophagy with 3-MA led to proliferation inhibition and increased apoptosis in HeLa cells, accompanied by the decreased LC3-I/II conversion and the increased active caspase-3. In conclusion, quercetin can inhibit HeLa cell proliferation and induce protective autophagy at low concentrations; thus, 3-MA plus quercetin would suppress autophagy and effectively increased apoptosis.

Keywords: Apoptosis; Autophagy; Cervical cancer; Quercetin.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis*
  • Autophagy*
  • Beclin-1 / metabolism
  • Caspase 3 / metabolism
  • Cell Proliferation
  • Female
  • HeLa Cells
  • Humans
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / metabolism
  • Phosphorylation
  • Quercetin / chemistry
  • Quercetin / pharmacology*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Beclin-1
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Quercetin
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • CASP3 protein, human
  • Caspase 3