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Curcumin sensitizes prostate cancer cells to tumor necrosis factor–related apoptosis-inducing ligand/Apo2L by inhibiting nuclear factor-κB through suppression of IκBα phosphorylation *

Epidemiologic studies suggest that diet rich in plant-derived foods plays an important role in the prevention of prostate cancer. Curcumin, the yellow pigment in the spice turmeric, has been shown to exhibit chemopreventive and growth inhibitory activities against multiple tumor cell lines. We have shown previously that curcumin and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)/Apo2L interact to induce cytotoxicity in the LNCaP prostate cancer cell line. In this study, we investigated the mechanism by which curcumin augments TRAIL-induced cytotoxicity in LNCaP cells. Subtoxic concentrations of the curcumin-TRAIL combination induced strong apoptotic response in LNCaP cells as demonstrated by the binding of Annexin V-FITC and cleavage of procaspase-3. Furthermore, LNCaP cells express constitutively active nuclear factor-κB (NF-κB), which is inhibited by curcumin. Because NF-κB has been shown to mediate resistance to TRAIL-induced apoptosis in tumor cells, we investigated whether there is a relationship between NF-κB activation and resistance to TRAIL in LNCaP prostate cancer cells. Pretreatment with curcumin inhibited the activation of NF-κB and sensitized LNCaP cells to TRAIL. A similar increase in the sensitivity of LNCaP cells to TRAIL-induced apoptosis was observed following inhibition of NF-κB by dominant negative mutant IκBα, an inhibitor of NF-κB. Finally, curcumin was found to inhibit NF-κB by blocking phosphorylation of IκBα. We conclude that NF-κB mediates resistance of LNCaP cells to TRAIL and that curcumin enhances the sensitivity of these tumor cells to TRAIL by inhibiting NF-κB activation by blocking phosphorylation of IκBα and its degradation.


* Legal Disclaimer: Chelation and Hyperbaric Therapy, Stem Cell Therapy, and other treatments and modalities mentioned or referred to in this web site are medical techniques that may or may not be considered “mainstream”. As with any medical treatment, results will vary among individuals, and there is no implication or guarantee that you will heal or achieve the same outcome as patients herein.

As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 06-05-2014