L-929 cells harboring ectopically expressed Re1A 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-kappa B (NF-kappa B)/Rel, a transcription factor that helps in cell survival. Signal-induced activation of NP-kappa B is known to be inhibited by curcumin. To understand the role of NF-kappa B in curcumin-induced apoptosis, we stably transfected relA gene encoding the p65/RelA subunit of NF-kappa B, 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-kappa B 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 I kappa B-alpha (known to inhibit NF-kappa B) 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-kappa B in curcumin-induced apoptosis.