Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity

被引:73
作者
Leu, TH
Su, SL
Chuang, YC
Maa, MC
机构
[1] Chung Shan Med Univ, Inst Biochem, Taichung, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan
关键词
curcumin; Src; Shc; ERK; FAK; migration; EPIDERMAL-GROWTH-FACTOR; PROTEIN-TYROSINE KINASE; PHOSPHORYLATION; RECEPTOR; IDENTIFICATION; AUTOPHOSPHORYLATION; OVEREXPRESSION; ENHANCEMENT; ACTIVATION; EXPRESSION;
D O I
10.1016/j.bcp.2003.08.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Curcumin (diferuloylmethane) is a well-known agent with anti-inflammatory, antioxidant, and anticarcinogenic properties. In this study, we observed that curcumin inhibited the kinase activity of v-Src, which led to a decrease in tyrosyl substrate phosphorylation of Shc, cortactin, and FAK. Our in vitro kinase experiment revealed that the inhibitory effect of curcumin on Src could be direct. Consistent with the abrogation of Src activity was the reduction of Src-Tyr-416 phosphorylation, Src-mediated Shc-Tyr-317 phosphorylation, decreased ERK activation, and cell proliferation in v-Src transformed cells. Remarkably, curcumin not only exerted its negative effect on FAK via the disappearance of Src-mediated FAK phosphorylation, but also directly inhibited its enzymatic activity. Concurrent to reduced cortactin tyrosyl phosphorylation and FAK kinase activity was the abolishment of v-Src-mediated cell mobility. To our knowledge, this is the first report indicating that curcumin can retard cellular growth and migration via downregulation of Src and FAK kinase activity. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:2323 / 2331
页数:9
相关论文
共 37 条
  • [1] Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells
    Agochiya, M
    Brunton, VG
    Owens, DW
    Parkinson, EK
    Paraskeva, C
    Keith, WN
    Frame, MC
    [J]. ONCOGENE, 1999, 18 (41) : 5646 - 5653
  • [2] Biscardi JS, 1999, ADV CANCER RES, V76, P61
  • [3] CALALB MB, 1995, MOL CELL BIOL, V15, P954
  • [4] STABLE ASSOCIATION OF PP60(SRC) AND PP59(FYN) WITH THE FOCAL ADHESION-ASSOCIATED PROTEIN-TYROSINE KINASE, PP125(FAK)
    COBB, BS
    SCHALLER, MD
    LEU, TH
    PARSONS, JT
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (01) : 147 - 155
  • [5] Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes
    Dinkova-Kostova, AT
    Talalay, P
    [J]. CARCINOGENESIS, 1999, 20 (05) : 911 - 914
  • [6] TURMERIC - CHEMISTRY, TECHNOLOGY, AND QUALITY
    GOVINDARAJAN, VS
    [J]. CRC CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, 1980, 12 (03): : 199 - 301
  • [7] Hong RL, 1999, CLIN CANCER RES, V5, P1884
  • [8] The role of tyrosine phosphorylation of cortactin in the locomotion of endothelial cells
    Huang, C
    Liu, JL
    Haudenschild, CC
    Zhan, X
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (40) : 25770 - 25776
  • [9] EFFECTS OF CURCUMIN, DEMETHOXYCURCUMIN, BISDEMETHOXYCURCUMIN AND TETRAHYDROCURCUMIN ON 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED TUMOR PROMOTION
    HUANG, MT
    MA, W
    LU, YP
    CHANG, RL
    FISHER, C
    MANCHAND, PS
    NEWMARK, HL
    CONNEY, AH
    [J]. CARCINOGENESIS, 1995, 16 (10) : 2493 - 2497
  • [10] MONOCLONAL-ANTIBODIES TO INDIVIDUAL TYROSINE-PHOSPHORYLATED PROTEIN SUBSTRATES OF ONCOGENE-ENCODED TYROSINE KINASES
    KANNER, SB
    REYNOLDS, AB
    VINES, RR
    PARSONS, JT
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (09) : 3328 - 3332