Sesamin manifests chemopreventive effects through the suppression of NF-κB-regulated cell survival, proliferation, invasion, and angiogenic gene products

Kuzhuvelil B. Harikumar, Bokyung Sung, Sheeja T. Tharakan, Manoj K. Pandey, Beena Joy, Sushovan Guha, Sunil Krishnan, Bharat B. Aggarwal

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Agents that are safe, affordable, and efficacious are urgently needed for the prevention of chronic diseases such as cancer. Sesamin, a lipid-soluble lignan, is one such agent that belongs to a class of phytoestrogens, isolated from sesame (Sesamum indicum), and has been linked with prevention of hyperlipidemia, hypertension, and carcinogenesis through an unknown mechanism. Because the transcription factor NF-κB has been associated with inflammation, carcinogenesis, tumor cell survival, proliferation, invasion, and angiogenesis of cancer, we postulated that sesamin might mediate its effect through the modulation of the NF-κB pathway. We found that sesamin inhibited the proliferation of a wide variety of tumor cells including leukemia, multiple myeloma, and cancers of the colon, prostate, breast, pancreas, and lung. Sesamin also potentiated tumor necrosis factor-α-induced apoptosis and this correlated with the suppression of gene products linked to cell survival (e.g., Bcl-2 and survivin), proliferation (e.g., cyclin D1), inflammation (e.g., cyclooxygenase-2), invasion (e.g., matrix metalloproteinase-9, intercellular adhesion molecule 1), and angiogenesis (e.g., vascular endothelial growth factor). Sesamin downregulated constitutive and inducible NF-κB activation induced by various inflammatory stimuli and carcinogens, and inhibited the degradation of IκBα, the inhibitor of NF-κB, through the suppression of phosphorylation of IκBα and inhibition of activation of IκBα protein kinase, thus resulting in the suppression of p65 phosphorylation and nuclear translocation, and NF-κB-mediated reporter gene transcription. The inhibition of IκBα protein kinase activation was found to be mediated through the inhibition of TAK1 kinase. Overall, our results showed that sesamin may have potential against cancer and other chronic diseases through the suppression of a pathway linked to the NF-κB signaling.

Original languageEnglish (US)
Pages (from-to)751-761
Number of pages11
JournalMolecular Cancer Research
Volume8
Issue number5
DOIs
StatePublished - May 2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

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