RETRACTED: Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of anglogenic factors and activation of CD8+ T cells in tumors (Retracted article. See vol. 94, pg. 618, 2018)

被引:48
作者
Mantena, SK
Roy, AM
Katiyar, SK
机构
[1] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL USA
[3] Birmingham VA Med Ctr, Birmingham, AL USA
关键词
D O I
10.1562/2005-04-11-RA-487
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG (approximate to 1 mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8(+) T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity.
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收藏
页码:1174 / 1179
页数:6
相关论文
共 27 条
[1]   VASCULAR ENDOTHELIAL GROWTH-FACTOR ACTS AS A SURVIVAL FACTOR FOR NEWLY FORMED RETINAL-VESSELS AND HAS IMPLICATIONS FOR RETINOPATHY OF PREMATURITY [J].
ALON, T ;
HEMO, I ;
ITIN, A ;
PEER, J ;
STONE, J ;
KESHET, E .
NATURE MEDICINE, 1995, 1 (10) :1024-1028
[2]   Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal [J].
Benjamin, LE ;
Golijanin, D ;
Itin, A ;
Pode, D ;
Keshet, E .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (02) :159-165
[3]   Vascular endothelial growth factor: Regulation in the mouse skin carcinogenesis model and use in antiangiogenesis cancer therapy [J].
Conti, CJ .
ONCOLOGIST, 2002, 7 :4-11
[4]   Ultraviolet radiation and tumor immunity [J].
de Gruijl, FR .
METHODS, 2002, 28 (01) :122-129
[5]   New functions for the matrix metalloproteinases in cancer progression [J].
Egeblad, M ;
Werb, Z .
NATURE REVIEWS CANCER, 2002, 2 (03) :161-174
[6]   The biology of vascular endothelial growth factor [J].
Ferrara, N ;
DavisSmyth, T .
ENDOCRINE REVIEWS, 1997, 18 (01) :4-25
[7]   Tumor invasion: molecular shears blunted by green tea [J].
Garbisa, S ;
Biggin, S ;
Cavallarin, N ;
Sartor, L ;
Benelli, R ;
Albini, A .
NATURE MEDICINE, 1999, 5 (11) :1216-1216
[8]   Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells [J].
Gerber, HP ;
Dixit, V ;
Ferrara, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) :13313-13316
[9]  
John Anitha, 2001, Pathology and Oncology Research, V7, P14
[10]   Clinical and histologic trends of melanoma [J].
Johnson, TM ;
Dolan, OM ;
Hamilton, TA ;
Lu, MC ;
Swanson, NA ;
Lowe, L .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1998, 38 (05) :681-686