Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB

Narendra P. Singh, Udai P. Singh, Venkatesh L. Hegde, Hongbing Guan, Lorne Hofseth, Mitzi Nagarkatti, Prakash S. Nagarkatti

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Scope: Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of resveratrol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth. Methods and results: Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of silent mating type information regulation 2 homolog, 1 (SIRT1) and downregulation of nuclear factor kappa B (NF-κB) in EL4 cells. siRNA-mediated downregulation of SIRT1 in EL4 cells increased the activation of NF-κB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-κB. Conclusion: These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-κB, leading to suppression of tumor growth.

Original languageEnglish (US)
Pages (from-to)1207-1218
Number of pages12
JournalMolecular Nutrition and Food Research
Volume55
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Apoptosis
  • Lymphoma
  • NF-κB
  • Resveratrol
  • SIRT1

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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