Antitumor activity of novel fluoro-substituted (-)-epigallocatechin-3-gallate analogs.
Epidemiological studies support the cancer-preventive effects of green tea and its main constituent (-)-epigallocatechin gallate [(-)-EGCG], however, (-)-EGCG is unstable under physiological conditions. Here we report that two novel fluoro-substituted (-)-EGCG analogs inhibited tumor growth with similar potency to that of Pro-EGCG (1) which has improved potency over parental compound (-)-EGCG in human breast cancer MDA-MB-231 xenografts. MDA-MB-231 tumors treated with each fluoro-substituted (-)-EGCG analog showed proteasome inhibition and apoptotic cell death, suggesting that the proteasome might be one of the cellular targets of fluoro-(-)-EGCGs and that proteasome inhibition is partially responsible for the observed antitumor activity.
Yang
Huanjie
H
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, MI, USA.
Sun
Dong Kui
DK
Chen
Di
D
Cui
Qiuzhi Cindy
QC
Gu
Yan Yan
YY
Jiang
Tao
T
Chen
Wei
W
Wan
Sheng Biao
SB
Dou
Q Ping
QP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D005461:Fluorine; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D061988:Proteasome Inhibitors; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D006845:Hydrocarbons, Fluorinated; D061988:Proteasome Inhibitors; C548750:pro-F-EGCG2; C548751:pro-F-EGCG4; D005461:Fluorine; D002392:Catechin; C045651:epigallocatechin gallate