Molecular mechanisms of curcumin action: Signal transduction

BioFactors - Tập 39 Số 1 - Trang 27-36 - 2013
Adeeb Shehzad1, Young Sup Lee1
1School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea

Tóm tắt

AbstractChemoprevention represents one of the most highly effective anti‐cancer strategies and is accompanied by minimal secondary effects as compared to conventional chemotherapies. Many new anti‐inflammatory and anti‐cancer drug candidates have been derived from chemical scaffolds engineered from natural products discovered just a few decades ago. This approach is widely utilized in drug discovery in order to produce novel molecular entities with enhanced drug activities mediated through various signal transduction pathways for the treatment of different diseases. Curcumin, a polyphenolic derivative of turmeric, is a naturally occurring compound isolated from Curcuma longa that suppresses and inverts carcinogenesis via multifaceted molecular targets. Several reports have demonstrated that curcumin inhibits animal and human cancers, suggesting that it may serve as a chemopreventive agent. Numerous in vitro and in vivo experimental models have also revealed that curcumin regulates several molecules in cell signal transduction pathway including NF‐κB, Akt, MAPK, p53, Nrf2, Notch‐1, JAK/STAT, β‐catenin, and AMPK. Modulation of cell signaling pathways through the pleiotropic effects of curcumin likely activate cell death signals and induce apoptosis in cancer cells, thereby inhibiting the progression of disease. This article provides insights into the natural chemopreventive role of curcumin via cellular transduction pathways and provides an in depth assessment of its physiological activities in the management of diseases. © 2013 BioFactors, 39(1):27–36, 2013

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Tài liệu tham khảo

10.1093/carcin/23.8.1307

Aggarwal B. B., 2003, Anticancer potential of curcumin: preclinical and clinical studies, Anticancer Res., 23, 363

10.1208/s12248-009-9128-x

10.2174/138161210791208956

10.1016/j.canlet.2008.03.025

10.1007/s00018-008-7452-4

10.1089/ars.2007.1769

10.1039/c1np00051a

10.1358/dof.2010.035.02.1426640

Ramachandran C., 2005, Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines, Anticancer Res., 25, 3293

Roy M., 2002, Induction of apoptosis in tumor cells by natural phenolic compounds, Asian Pac. J. Cancer Prev., 3, 61

10.1200/JCO.2007.15.7198

10.1152/physrev.00015.2006

10.1038/sj.onc.1210638

10.1016/j.canlet.2008.06.031

Wu S. H., 2010, Curcumin induces apoptosis in human non‐small cell lung cancer NCI‐H460 cells through ER stress and caspase cascade‐ and mitochondria‐dependent pathways, Anticancer Res., 30, 2125

10.1155/2012/512907

10.1158/1535-7163.MCT-10-0812

Guo L. D., Curcumin inhibits proliferation and induces apoptosis of human colorectal cancer cells by activating the mitochondria apoptotic pathway, Phytother. Res.

10.1093/carcin/bgg082

10.1006/excr.2001.5381

10.1093/carcin/bgi089

10.1074/jbc.M601553200

10.1016/j.intimp.2012.04.002

10.1186/1750-2187-2-10

10.1093/carcin/23.1.143

10.1016/S0891-5849(01)00629-3

10.1016/S0014-5793(03)00099-1

10.1016/j.bbrc.2011.07.044

10.1128/MCB.24.15.6728-6741.2004

10.1038/sj.onc.1208615

10.1093/carcin/bgh163

10.3892/ijmm_00000513

Liontas A., 2004, Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma, Anticancer Res., 24, 987

10.1016/S0092-8674(00)80416-X

10.1006/bbrc.2001.5627

Pan W., 2008, AMPK mediates curcumin‐induced cell death in CaOV3 ovarian cancer cells, Oncol. Rep., 20, 1553

10.1016/j.canlet.2010.04.018

Wang M. E., Curcumin protects against thioacetamide‐induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes, J. Nutr. Biochem.

10.3109/07357907.2010.550592

10.1002/ijc.20333

10.1158/1940-6207.CAPR-09-0076

10.1002/ijc.25220

10.1111/j.1601-0825.2006.01334.x

10.1002/ptr.2989

10.1101/gad.1228704

10.1182/blood-2002-05-1320

10.1021/np200666t

10.1016/S0027-5107(01)00182-8

10.1038/labinvest.3700532

10.1093/carcin/bgg107

10.1152/ajpgi.00449.2002

10.1016/j.ejps.2012.04.018

Shehzad A., Curcumin therapeutic promises and bioavailability in colorectal cancer, Drugs Today (Barc), 46, 523, 10.1358/dot.2010.46.7.1509560

10.1186/bcr596

10.1158/1535-7163.MCT-07-2400

10.1111/j.1749-6632.2009.04699.x

10.1016/S0006-2952(02)01517-4

10.1124/jpet.106.117721

Wang H., Curcumin potentiates antitumor activity of l‐asparaginase via inhibition of the AKT signaling pathway in acute lymphoblastic leukemia, Leuk. Lymphoma., 53, 1376, 10.3109/10428194.2011.649478

10.1128/MCB.00630-07

Wang Z., 2008, Exploitation of the Notch signaling pathway as a novel target for cancer therapy, Anticancer Res., 28, 3621

10.1002/jcb.23019

10.1016/j.otohns.2008.12.057

10.1371/journal.pone.0030590

10.1002/cncr.21904

10.1111/j.1742-4658.2012.08607.x

10.1016/j.mam.2011.10.006

10.1016/j.freeradbiomed.2011.11.038

10.1007/s11064-008-9608-x

Shehzad A., New mechanisms and the anti‐inflammatory role of curcumin in obesity and obesity‐related metabolic diseases, Eur. J. Nutr., 50, 151, 10.1007/s00394-011-0188-1

10.1155/2012/269039

10.4239/wjd.v3.i5.94

10.5754/hge11219

10.1016/j.gene.2004.06.044

10.2174/156800910793605794

10.1016/j.devcel.2005.03.016

10.1016/j.cbi.2009.06.012

10.1371/journal.pone.0035368

10.1002/jnr.1169

10.1093/emboj/20.1.91

10.1182/blood-2002-05-1521

10.1634/stemcells.19-5-378

10.1074/jbc.M203885200

10.4049/jimmunol.171.11.6072

10.1016/j.canlet.2009.06.023

10.1007/s00395-012-0263-7

10.1126/science.1164551

10.1371/journal.pone.0023194

10.1016/j.cmet.2004.12.003

10.1042/CS20110625

10.1158/0008-5472.CAN-06-1814

10.1007/s00109-011-0748-0

10.1002/jcp.22691

10.1021/jf802737z

10.1080/01635581.2012.630554

10.1016/j.bbamcr.2006.11.004

10.1016/j.taap.2012.05.012

10.1016/j.bpc.2009.12.007

10.1074/jbc.M409024200