L-929 cells harboring ectopically expressed RelA resist curcumin-induced apoptosis.
Curcumin (diferuloyl methane), the yellow pigment in turmeric (Curcuma longa), is a potent chemopreventive agent. Curcumin induces apoptosis of several, but not all, cancer cells. Many cancer cells protect themselves against apoptosis by activating nuclear factor-kappaB (NF-kappaB)/Rel, a transcription factor that helps in cell survival. Signal-induced activation of NF-kappaB is known to be inhibited by curcumin. To understand the role of NF-kappaB in curcumin-induced apoptosis, we stably transfected relA gene encoding the p65/RelA subunit of NF-kappaB, into l-929 cells (mouse fibrosarcoma) and the relA-transfected cells were resistant to varying doses of curcumin (10(-6)-10(-4) m), whereas the parental cells underwent apoptosis in a time- and dose-dependent manner. The relA-transfected cells showed constitutive NF-kappaB DNA binding activity that could not be inhibited by curcumin and did not show nuclear condensation and DNA fragmentation upon treatment with curcumin. When a super-repressor form of IkappaB-alpha (known to inhibit NF-kappaB) was transfected transiently into relA-transfected cells, the cells were no longer resistant to curcumin. Our results highlight a critical anti-apoptotic role for NF-kappaB in curcumin-induced apoptosis.
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Division of Cancer Biology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala-695014, India.
Maliekal
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Karunagaran
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D051996:Transcription Factor RelA; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D003474:Curcumin