Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

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-kB. 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. Ó2012 AACR.

Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells

“…Our findings demonstrated that the degradation of Beclin-1 occurred especially at 24 h of curcumin treatment. Similar results were obtained in cutaneous T-cell lymphoma (HuT-78) [54]. In addition, the expression level of Atg5 was found to be more stable than that of Beclin-1 in both cell lines Fig.…”

Ceramide generation during curcumin-induced apoptosis is controlled by crosstalk among Bcl-2, Bcl-xL, caspases and glutathione

“…Upstream, the GSH reduction in HL-60 cells is controlled by caspase-8 but not caspase-3, yet it affects both enzymes (Fig. 6A, B), similarly as during apoptosis induced by TNF-α in MCF7 cells and by curcumin in HuT-78 cells [27,65]. The curcumin-induced GSH depletion in HL-60 cells is also in mutual regulation with Bcl-2 and Bcl-xL similarly as shown earlier [27,45,65].…”

Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy

“…the presence of the broad-range caspase inhibitor z-VAD-fmk, a reduction of caspase-3 activation was observed but there was no significant decrease on cytochrome C release [75].…”