Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch‐1 signaling

FEBS Journal - Tập 279 Số 12 - Trang 2247-2259 - 2012
Yonggang Li1, Jingru Zhang2, Daoxin Ma2, Lei Zhang1, Meng Si1, Han Yin1, Jianmin Li1
1Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, China
2Department of Hematology, Qilu Hospital, Shandong University, Jinan, China

Tóm tắt

The Notch signaling pathway plays critical roles in human cancers, including osteosarcoma, suggesting that the discovery of specific agents targeting Notch would be extremely valuable for osteosarcoma. Curcumin, a naturally occurring phenolic compound found in curcuma longa, has been shown to inhibit proliferation and induce apoptosis of osteosarcoma cells in vitro and tumor growth in xenotransplant or orthotransplant models. However, the precise molecular mechanisms by which curcumin exerts its antitumor activity remain unclear. Here we used multiple molecular approaches, such as the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, the invasion assay, gene transfection, real‐time RT‐PCR, western blot and gelatin zymography, to investigate whether the downregulation of Notch‐1 contributes to curcumin‐induced inhibition of proliferation and invasion in osteosarcoma cells. The results showed that curcumin caused marked inhibition of osteosarcoma cell growth and G2/M phase cell cycle arrest. This was associated with concomitant attenuation of Notch‐1 and downregulation of its downstream genes, such as matrix metalloproteinases, resulting in the inhibition of osteosarcoma cell invasion through Matrigel. We also found that specific downregulation of Notch‐1 via small‐interfering RNA prior to curcumin treatment resulted in enhanced inhibition of cell growth and invasion. These results suggest that antitumor activity of curcumin is mediated through a novel mechanism involving inactivation of the Notch‐1 signaling pathway. Our data provide the first evidence that the downregulation of Notch‐1 by curcumin may be an effective approach for the treatment of osteosarcoma.

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Tài liệu tham khảo

10.1200/JCO.2005.03.5352

10.1200/JCO.2002.20.3.776

10.1093/jjco/hyp057

10.1016/j.ccr.2005.06.013

10.1016/j.gde.2003.11.004

10.1126/science.1134042

10.1182/blood-2005-08-3329

10.1158/1535-7163.MCT-05-0299

10.1016/j.ygyno.2006.08.054

Katoh M, 2007, Notch signaling in gastrointestinal tract (review), Int J Oncol, 30, 247

10.1093/hmg/ddp057

10.1158/1078-0432.CCR-07-1992

10.1038/sj.bjc.6605060

10.1080/01635580903285106

10.1158/1940-6207.CAPR-09-0076

10.1002/cncr.21904

10.1007/s10637-007-9099-7

10.1021/jf9024807

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

10.1016/j.canlet.2008.03.009

10.1016/j.bcp.2006.02.009

Lin HJ, 2010, Curcumin blocks migration and invasion of mouse‐rat hybrid retina ganglion cells (N18) through the inhibition of MMP‐2, ‐9, FAK, Rho A and Rock‐1 gene expression, Oncol Rep, 23, 665

10.1016/j.canlet.2009.04.037

Lee DS, 2009, Curcumin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS) cells, Anticancer Res, 29, 5039

10.1007/s10637-009-9311-z

10.1007/BF03032599

10.1016/S1055-3207(18)30071-1

10.1158/0008-5472.CAN-05-4281

Wang J, 2011, Notch1 is involved in migration and invasion of human breast cancer cells, Oncol Rep, 26, 1295

Yu B, 2012, Notch1 signaling pathway participates in cancer invasion by regulating MMPs in lingual squamous cell carcinoma, Oncol Rep, 27, 547

10.1053/j.gastro.2011.06.056

Qi R, 2003, Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis, Cancer Res, 63, 8323

10.1007/978-1-4419-0284-9_28

10.1016/S0002-9440(10)61121-2

10.1002/jcp.10467

10.1002/pros.1074

10.1093/carcin/19.9.1697

10.1016/S0022-2143(97)90107-4

10.1158/1535-7163.MCT-07-2400

10.1186/1471-2407-11-112

10.1002/jcb.23184

10.5483/BMBRep.2007.40.6.1069

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FEBS Journal

Tập 279 Số 12

2247-2259

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