Inhibitory effects of asiatic acid on 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice.
Asiatic acid, a pentacyclic triterpene, has been reported to induce apoptosis of various human cancer cells. In the present study, we assessed the anti-tumor promoting effect of asiatic acid against 12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated skin tumorigenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated ICR mice. Topical application of asiatic acid prior to each application of TPA resulted in a significant reduction in skin tumor formation. We also found that pre-application of asiatic acid alleviated TPA-induced [3H]thymidine incorporation, which is a conventional marker for skin tumor promotion. In addition, asiatic acid inhibited the TPA-induced generation of nitric oxide (NO) and expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are known to play important roles in tumor growth, especially in the promotion stage. In addition, topical application of aminoguanidine (AG), a selective iNOS inhibitor, and N(G)-nitro-L-arginine-methyl ester (NAME), another iNOS inhibitor, 30 min prior to TPA treatment significantly inhibited the TPA-induced COX-2 expression. These results suggest that asiatic acid may exert anti-tumorigenesis through inhibitory actions in NO and COX-2 signals.
Park
Byung Chul
BC
College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Paek
Seung-Hwan
SH
Lee
Yoon-Seok
YS
Kim
Seung-Joo
SJ
Lee
Eung-Seok
ES
Choi
Han Gon
HG
Yong
Chul Soon
CS
Kim
Jung-Ae
JA
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003043:Cocarcinogenesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D053978:Pentacyclic Triterpenes; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D009569:Nitric Oxide; D015127:9,10-Dimethyl-1,2-benzanthracene; C017032:asiatic acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate