Carcinogenesis Advance Access published online on June 17, 2004
Carcinogenesis, doi:10.1093/carcin/bgh213
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Cancer Biology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, India
* To whom correspondence should be addressed. E-mail: dkarunagaran{at}hotmail.com.
Curcumin, the yellow pigment derived from Curcuma longa, is known to induce apoptosis of several cancer cells. However, many cancer cells protect themselves by overexpressing antiapoptotic proteins such as Bcl-XL or Ku70. To study their role in curcumin-induced apoptosis, human colon cancer cells (SW480) were made to overexpress or underexpress Bcl-XL (by stable transfection) and Ku70 (by transient transfection) using plasmid construts that express their genes in sense or antisense orientation, respectively. Stable cells that express Bax (Bax-GFP), a proapoptotic member of the Bcl-2 family, were also established. Curcumin-induced cell death and nuclear condensation were more in AsBcl-XL and AsKu70 cells that underexpress Bcl-XL and Ku70, respectively, compared to the vector-transfected cells. Bcl-XL and Ku70 protected the cells by inhibiting the release of cytochrome c, Smac and AIF, and the activation of caspases 9, 8 and 3 triggered by curcumin. AsBcl-XL and AsKu70 cells were more sensitive to curcumin through enhanced activation of caspases 9 and 3 and release of cytochrome c, Smac and AIF. Curcumin-induced activation of caspase 8 was blocked by Ku70 but not by Bcl-XL. However, caspase 8 activation by curcumin was accelerated in both AsBcl-XL and AsKu70 cells suggesting a possible feedback activation of caspase 8 by caspase 3. Bax-GFP cells were highly sensitized when Ku70 was downregulated supporting the reported role of Ku70 in the retention of Bax within the cytosol. The study reveals the potential of antisense inhibition of antiapoptotic proteins as an effective strategy to tackle chemoresistant cancers with curcumin.
Revised May 29, 2004
Accepted June 6, 2004
CANCER BIOLOGY
Ectopic expression of Bcl-XL or Ku70 protects human colon cancer cells (SW480) against curcumin-induced apoptosis while their downregulation potentiates it
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Salvioli, E. Sikora, E. L. Cooper, and C. Franceschi Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies Evid. Based Complement. Altern. Med., June 1, 2007; 4(2): 181 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-L. Hsiao, W.-S. Wang, P.-M. Chen, and Y. Su Overexpression of thymosin {beta}-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively Carcinogenesis, May 1, 2006; 27(5): 936 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Subramanian, A. W. Opipari Jr., X. Bian, V. P. Castle, and R. P. S. Kwok Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors PNAS, March 29, 2005; 102(13): 4842 - 4847. [Abstract] [Full Text] [PDF]
|
|