PT  - JOURNAL ARTICLE
AU  - Khan, Mohammad Aslam
AU  - Gahlot, Satindra
AU  - Majumdar, Sekhar
TI  - Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets
AID  - 10.1158/1535-7163.MCT-12-0141
DP  - 2012 Sep 01
TA  - Molecular Cancer Therapeutics
PG  - 1873--1883
VI  - 11
IP  - 9
4099  - http://mct.aacrjournals.org/content/11/9/1873.short
4100  - http://mct.aacrjournals.org/content/11/9/1873.full
SO  - Mol Cancer Ther2012 Sep 01; 11
AB  - 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. Mol Cancer Ther; 11(9); 1873–83. ©2012 AACR.