Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation

Eur J Pharmacol. 2019 Oct 5:860:172568. doi: 10.1016/j.ejphar.2019.172568. Epub 2019 Jul 23.

Abstract

In this study, we investigated whether Quercetin has anti-cancer effects on A375SM and A375P human melanoma cells. Cell viability was assessed using an MTT assay. The proliferation of melanoma cells was measured by a wound-healing assay. Quercetin significantly decreased viability and proliferation of A375SM cells in a concentration-dependent manner. However, quercetin had no effect on A375P cells. DAPI staining showed increased chromatin condensation in a concentration-dependent manner, indicating apoptosis. Flow cytometric analysis indicated that quercetin suppressed the viability of A375SM cells by inducing apoptosis. Expression of quercetin-induced apoptosis proteins was investigated by Western blot analysis. Quercetin increased the expression of Bax, phospho-JNK, phospho-p38 and phospho-ERK1/2, cleaved poly-ADP ribose polymerase and decreased Bcl-2 in a concentration-dependent manner. We also investigated the in vivo tumor-growth inhibitory effect of quercetin. Quercetin (at 50 and 100 mg/kg) significantly decreased the A375SM tumor volume compared to the control group and increased apoptosis as assessed by the TUNEL assay. Immunohistochemistry staining revealed that the level of phosphor-JNK and phosphor-p38 increased in the quercetin-treated mice. These results indicate that quercetin inhibited the growth of A375SM melanoma cells through apoptosis and thus can be regarded as a new and effective chemo-preventive or therapeutic agent.

Keywords: Antitumor; Apoptosis; JNK/P38; Melanoma cells; Quercetin.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / drug effects*
  • Melanoma / pathology*
  • Mice
  • Quercetin / pharmacology*
  • Xenograft Model Antitumor Assays
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Quercetin
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases