Enhanced antitumor activities of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives in vitro and in vivo.
(-)-Epigallocatechin-3-O-gallate (EGCG) monoesters modified with butanoyl (EGCG-C4), octanoyl (EGCG-C8), palmitoyl groups (EGCG-C16) were synthesized by a lipase-catalyzed transesterification method and their antitumor activities were investigated in vitro and in vivo. The in vitro antitumor activities of EGCG-monoester derivatives increased in an alkyl chain length-dependent manner. The cytotoxicity of EGCG, EGCG-C4, EGCG-C8 was mainly caused by H(2)O(2) which was generated with their oxidation. On the other hand, EGCG-C16 was more stable than EGCG and it did not generate H(2)O(2) in the cell culture medium. Furthermore, EGCG-C16 inhibited cell proliferation and induced apoptosis in the presence of catalase. EGCG-C16 was found to inhibit the phosphorylation of the epidermal growth factor receptor (EGFR), which is related to various types of tumor growth. EGCG-C16 suppressed tumor growth in vivo in colorectal tumor bearing mice in comparison to an untreated control, vector control (DMSO) and EGCG.
Matsumura
Kazuaki
K
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Kaihatsu
Kunihiro
K
Mori
Shuichi
S
Cho
Han Hee
HH
Kato
Nobuo
N
Hyon
Suong Hyu
SH
D000215:Acylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005227:Fatty Acids; D002392:Catechin; C045651:epigallocatechin gallate