Related Experiment Video

Updated: Jul 7, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

Resveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression

Vladimir N Ivanov1, Michael A Partridge, Geoffrey E Johnson

  • 1Center for Radiological Research, Columbia University, New York, NY 10032, USA. vni3@columbia.edu

Experimental Cell Research
|January 29, 2008
PubMed

Insights

Resveratrol enhances TRAIL therapy for melanoma by suppressing anti-apoptotic proteins cFLIP and Bcl-xL. Combining resveratrol with TRAIL may offer an effective treatment for melanoma by reactivating cancer cell death pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Human melanomas often resist TRAIL-induced apoptosis due to elevated STAT3/NF-kappaB signaling.
  • This signaling pathway upregulates anti-apoptotic proteins like cFLIP and Bcl-xL, contributing to TRAIL resistance.
  • The JNK-cJun pathway negatively regulates cFLIP, a key inhibitor of apoptosis.

Purpose of the Study:

  • To investigate the potential of resveratrol in overcoming TRAIL resistance in human melanomas.
  • To elucidate the molecular mechanisms by which resveratrol sensitizes melanoma cells to TRAIL.
  • To explore combination strategies involving resveratrol and TRAIL for melanoma treatment.

Main Methods:

  • Assessing the effects of resveratrol on STAT3, NF-kappaB, and JNK-cJun pathways in melanoma cells.
  • Measuring the expression levels of cFLIP and Bcl-xL proteins.
  • Evaluating melanoma cell sensitivity to TRAIL following resveratrol treatment.
  • Investigating the impact of gamma-irradiation and sodium arsenite on DR5 expression.

Main Results:

  • Resveratrol decreased STAT3/NF-kappaB activation and increased JNK-cJun pathway activity.
  • This modulation by resveratrol led to suppressed cFLIP and Bcl-xL expression, enhancing TRAIL sensitivity in DR5-positive melanomas.
  • Resveratrol did not alter surface DR5 expression, unlike gamma-irradiation or sodium arsenite which increased it.
  • A combination of increased DR5 expression and resveratrol-induced suppression of cFLIP/Bcl-xL shows promise for reactivating apoptosis.

Conclusions:

  • Resveratrol can overcome TRAIL resistance in melanomas by downregulating anti-apoptotic proteins.
  • Combining strategies that increase DR5 surface expression with resveratrol may be an effective approach for melanoma treatment.
  • Resveratrol, in conjunction with TRAIL, demonstrates significant potential for treating human melanomas by reactivating apoptotic pathways.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...