Prevention by 1'-acetoxychavicol acetate of the induction but not growth of putative preneoplastic, glutathione S-transferase placental form-positive, focal lesions in the livers of rats fed a choline- deficient, L-amino acid-defined diet

Abstract

The effects of 1'-acetoxychavicol acetate (ACA) on endogenous rat liver carcinogenesis because of chronic feeding of a choline-deficient, L-amino acid-defined (CDAA) diet were examined. Male Fischer 344 rats, 6 weeks old, received the CDAA diet containing ACA at doses of 0, 0.005, 0.010 and 0.050% for 12 weeks and were then killed. ACA decreased the numbers of putative preneoplastic, glutathione S-transferase placental form (GST-P)-positive, focal lesions developing in the livers of rats fed the CDAA diet but did not alter their sizes. At the same time, ACA reduced the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, but did not significantly affect generation of 2-thiobarbituric acid-reacting substances, indicators of oxidative extra-DNA damage, or hepatocyte proliferation. Furthermore, ACA did not exert any significant effects on the numbers or sizes of GST-P-positive lesions in the livers of rats when administered between weeks 2 and 8 after initiation with a single i.p. dose of 200 mg/kg body wt of N-nitrosodiethylamine. These results indicate that ACA prevents the CDAA diet-associated induction of putative preneoplastic lesions by reduction of oxidative DNA damage but does not affect their subsequent growth.

Alterations of the Transforming Growth Factor‐(β Signaling Pathway in Hepatocellular Carcinomas Induced Endogenously and Exogenously in Rats

“…We have reported that a cell cycle disturbance induced in DEN-initiated hepatocytes by colchicine gives a growth advantage to formation of putative preneoplastic lesions under conditions of partial hepatectomy (PH) and selection pressure, so that a high incidence of HCCs can be obtained within a short period. 3,4) Since our studies revealed differential effects of chemopreventive agents in our two liver models, 5,6) the possibility arises of different mechanisms underlying endogenous and exogenous hepatocarcinogenesis in rats.…”

Identification of a Novel Blocker of IκBα Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-κB-Regulated Gene Products

“…One of these, 1Ј-acetoxychavicol acetate (ACA), 3 derived from the rhizomes of a subtropical ginger, Languas galanga Stuntz (Zingiberaceae), has been shown to exhibit antitumor properties against a wide variety of cancers (2)(3)(4)(5)(6)(7)(8)(9)(10). For instance, ACA has been shown to inhibit phorbol ester-induced skin tumor promotion (8), azoxymethane-induced colonic aberrant crypt foci (7), estrogen-related endometrial carcinogenesis (6), hepatic focal lesions (5), rat oral carcinogenesis (4), and N-nitrosomethylbenzylamineinduced rat esophageal tumorigenesis (3).…”

Inhibitory Effects of 1′‐Acetoxychavicol Acetate on N‐Nitrosobis(2‐oxopropyl)‐amine‐induced Initiation of Cholangiocarcinogenesis in Syrian Hamsters

“…22) ACA has been shown to reduce the level of 8-hydroxyguanine in the liver caused by dietary choline deficiency. 6) In addition, it is reported to suppress nitric oxide production in a murine macrophage cell line stimulated with lipopolysaccharide or interferon-γ. 23) Since reactive oxygen or nitrogen species are believed to contribute to carcinogenic processes, [24][25][26][27] it is likely that ACA could exert an inhibitory effect partly through inhibition of superoxide generation.…”

“…1) ACA has been extensively investigated for chemopreventive action in rodent carcinogenesis models. [2][3][4][5][6] It was shown to inhibit 12-O-tetradecanoylphorbol-13-acetate promotion of skin carcinogenesis in female ICR mice initiated with 7,12-dimethylbenz[a]anthracene, 2) 4-nitroquinoline-1-oxide (4-NQO)-induced oral tumor development 3) and azoxymethane (AOM)-induced colon carcinogenesis during both initiation and post-initiation phases, 4,5) as well as choline-deficient, L-amino acid-defined diet-associated induction of glutathione S-transferase-positive liver lesions in male F344 rats. 6) In addition, ACA was demonstrated to inhibit xanthine oxidase, which generates superoxide anions known to be associated with tumor promotion, 7) and also to inhibit tumor promoter-induced Epstein-Barr virus activation in vitro.…”