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J. Biol. Chem., Vol. 275, Issue 21, 15601-15604, May 26, 2000
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From the Division of Cancer Biology, Rajiv Gandhi Center
for Biotechnology, Thiruvananthapuram, Kerala-695014, India
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-
ACCELERATED PUBLICATION
L-929 Cells Harboring Ectopically Expressed RelA Resist
Curcumin-induced Apoptosis*
, and
B (NF-B)/Rel, a transcription factor
that helps in cell survival. Signal-induced activation of NF-B is
known to be inhibited by curcumin. To understand the role of NF-B in curcumin-induced apoptosis, we stably transfected relA gene
encoding the p65/RelA subunit of NF-B, into L-929 cells
(mouse fibrosarcoma) and the relA-transfected cells were
resistant to varying doses of curcumin
(10
6-104 M), whereas the
parental cells underwent apoptosis in a time- and
dose-dependent manner. The relA-transfected
cells showed constitutive NF-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 IB-
(known to inhibit NF-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-B in curcumin-induced apoptosis.
*
This work was supported by core grants to the Rajiv Gandhi
Center for Biotechnology from the Department of Biotechnology, Government of India and the Science, Technology and Environment Committee, Government of Kerala, India.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a Senior Research Fellowship from the Council of
Scientific and Industrial Research, India.
§
To whom correspondence should be addressed. Tel.: 91-471-323003;
Fax: 91-471-329472; E-mail: dkarunagaran@hotmail.com.
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