Khan, Mohammad Aslam and Gahlot, Satindra and Majumdar, Sekhar (2012) Oxidative stress induced by curcumin promotes the death of cutaneous T-cell lymphoma (HuT-78) by disrupting the function of several molecular targets. Molecular cancer therapeutics, 11 (9). pp. 1873-83. ISSN 1538-8514
Full text not available from this repository. (Request a copy)Abstract
Curcumin is known to exert its anticancer effect either by scavenging or by generating reactive oxygen species (ROS). In this study, we report that curcumin-mediated rapid generation of ROS induces apoptosis by modulating different cell survival and cell death pathways in HuT-78 cells. Curcumin induces the activation of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but the addition of caspase inhibitors only partially blocked the curcumin-mediated apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c-FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS-dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF-κB. Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to AACR. |
| Uncontrolled Keywords: | Therapeutic Discovery |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 28 Jan 2013 11:49 |
| Last Modified: | 28 Jan 2013 11:49 |
| URI: | http://crdd.osdd.net/open/id/eprint/1243 |
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