Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispen.pdfVIP
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Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispen
Human colon cancer cells lacking Bax resist curcumin-induced apoptosis
and Bax requirement is dispensable with ectopic expression of Smac
or downregulation of Bcl-XL
Ramachandran Rashmi, Santhosh Kumar
and Devarajan Karunagaran
Cancer Biology Laboratory, Rajiv Gandhi Centre for Biotechnology,
Thiruvananthapuram, Kerala 695 014, India
To whom correspondence should be addressed. Tel: t91 471 2347975;
Fax: t91 471 2348096;
E-mail: dkarunagaran@
Multiple apoptotic stimuli induce conformational changes
in Bax, a proapoptotic protein from the Bcl-2 family and
its deficiency is a frequent cause of chemoresistance in
colon adenocarcinomas. Curcumin, a dietary compound
from turmeric, is known to induce apoptosis in a variety
of cancer cells. To understand the role of Bax in curcumin-
induced apoptosis we used HCT116 human colon cancer
cells with one allele of Bax gene (Baxt/) and Bax knockout
HCT116 (Bax/) cells in which Bax gene is inactivated by
homologous recombination. Cell viability decreased in a
concentration-dependent manner in Baxt/ cells treated
with curcumin (0--50 mM) whereas only minimal changes
in viability were observed in Bax/ cells upon curcumin
treatment. In Bax/ cells curcumin-induced activation
of caspases 9 and 3 was blocked and that of caspase 8
remained unaltered. Curcumin-induced release of cyto-
chrome c, Second mitochondria derived activator of cas-
pase (Smac) and apoptosis inducing factor (AIF) was also
blocked in Bax/ cells and reintroduction of Bax, down-
regulation of the antiapoptotic protein Bcl-XL by antisense
DNA as well as the overexpression of Smac, highly sensit-
ized the Bax/ cells toward curcumin-induced apoptosis.
There was no considerable difference in the percentage of
apoptotic cells in Bak RNAi transfected Baxt/ or Bax/
cells treated with curcumin when compared with their
corresponding vector transfected cells treated with curcu-
min. The present study demonstrates the role of Bax but
not Bak as a critical regulat
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