Resveratrol induces cell-cycle disruption and apoptosis in chemoresistant B16 melanoma

Grégory Gatouillat1, Emilie Balasse, Débora Joseph-Pietras

  • 1Faculty of Pharmacy, Department of Biochemistry and Molecular Biology, URCA, Reims, France.

Insights

Resveratrol inhibits the growth of chemoresistant melanoma by halting cell cycle progression and inducing apoptosis. This natural compound also enhances doxorubicin

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Resveratrol, a polyphenol, exhibits chemopreventive properties.
  • Chemotherapeutic resistance, particularly to doxorubicin, is a significant clinical challenge in melanoma treatment.

Purpose of the Study:

  • To investigate the efficacy of resveratrol against doxorubicin-resistant B16 melanoma.
  • To elucidate the mechanisms underlying resveratrol's anti-cancer effects.
  • To evaluate resveratrol's therapeutic potential in vivo.

Main Methods:

  • Cell culture of doxorubicin-resistant B16 melanoma (B16/DOX) cells.
  • Resveratrol treatment and assessment of cell viability (IC50 determination).
  • Cell cycle analysis, Western blotting for cyclin D1/cdk4 and p53 expression.
  • Apoptosis assays (nuclear morphology, DNA fragmentation).
  • In vivo studies using a mouse melanoma model.

Main Results:

  • Resveratrol inhibited B16/DOX cell growth with an IC50 of 25 microM.
  • Resveratrol induced G1-S phase arrest by down-regulating cyclin D1/cdk4 and up-regulating p53.
  • Resveratrol triggered apoptosis in B16/DOX cells.
  • Resveratrol potentiated doxorubicin cytotoxicity in chemoresistant melanoma.
  • In vivo, resveratrol reduced tumor growth and prolonged survival in mice.

Conclusions:

  • Resveratrol demonstrates significant anti-cancer activity against chemoresistant melanoma.
  • Resveratrol's mechanism involves cell cycle arrest and apoptosis induction.
  • Resveratrol holds potential as a therapeutic agent for chemoresistant melanoma, alone or in combination therapy.

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