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Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines *

Curcumin has potential as a chemopreventative and chemotherapeutic agent, but its interactions with clinically relevant cytokines are poorly characterized. Because cytokine immunotherapy is a mainstay of treatment for malignant melanoma, we hypothesized that curcumin could modulate the cellular responsiveness to interferons and interleukins. As a single agent, curcumin induced a dose-dependent increase in apoptosis of human melanoma cell lines, which was most prominent at doses >10 μmol/L. Immunoblot analysis confirmed that curcumin induced apoptosis and revealed caspase-3 processing, poly ADP ribose polymerase cleavage, reduced Bcl-2, and decreased basal phosphorylated signal transducers and activators of transcription 3 (STAT3). Despite its proapoptotic effects, curcumin pretreatment of human melanoma cell lines inhibited the phosphorylation of STAT1 protein and downstream gene transcription following IFN-α and IFN-γ as determined by immunoblot analysis and real time PCR, respectively. Pretreatment of peripheral blood mononuclear cells from healthy donors with curcumin also inhibited the ability of IFN-α, IFN-γ, and interleukin-2 to phosphorylate STAT proteins critical for their antitumor activity (STAT1 and STAT5, respectively) and their respective downstream gene expression as measured by real time PCR. Finally, stimulation of natural killer (NK) cells with curcumin reduced the level of interleukin-12–induced IFN-γ secretion, and production of granzyme b or IFN-γ upon coculture with A375 melanoma cells or NK-sensitive K562 cells as targets. These data show that although curcumin can induce apoptosis of melanoma cells, it can also adversely affect the responsiveness of immune effector cells to clinically relevant cytokines that possess antitumor properties. [Mol Cancer Ther 2009;8(9):2726–35]

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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 12-23-2010
Authors: Matthew A. Bill, Courtney Bakan, Don M. Benson, Jr., James Fuchs, Gregory Young and Gregory B. Lesinski
Source: Published OnlineFirst September 1, 2009; doi: 10.1158/1535-7163.MCT-09-0377