Purple corn color suppresses Ras protein level and inhibits 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in the rat.
Anthocyanins belong to the class of phenolic compounds collectively named flavonoids. Many anthocyanins are reported to have inhibitory effects on carcinogenesis. Purple corn color (PCC), an anthocyanin containing extract of purple corn seeds, is used as a food colorant. The major anthocyanin in PCC is cyanidin 3-O-beta-D-glucoside (C3-G). The present study was conducted to assess the influence of dietary PCC on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats. PCC significantly inhibited DMBA-induced mammary carcinogenesis in human c-Ha-ras proto-oncogene transgenic (Hras128) rats and in their non-transgenic counterparts. PCC and C3-G also inhibited cell viability and induced apoptosis in mammary tumor cells derived from Hras128 rat mammary carcinomas. At the molecular level, PCC and C3-G treatment resulted in a preferential activation of caspase-3 and reduction of Ras protein levels in tumor cells. It is proposed that C3-G could act as a chemopreventive and possibly chemotherapeutic agent for cancers with mutations in ras. Secondly, the in vitro-in vivo system used in this study can be utilized for screening for cancer preventive compounds that act via Ras down-regulation.
Fukamachi
Katsumi
K
Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Imada
Takafumi
T
Ohshima
Yutaka
Y
Xu
Jiegou
J
Tsuda
Hiroyuki
H
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051381:Rats; D003313:Zea mays; D018631:ras Proteins / Q000378:metabolism*
D000872:Anthocyanins; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D005960:Glucosides; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C462279:cyanidin-3-O-beta-glucopyranoside; D015127:9,10-Dimethyl-1,2-benzanthracene; D053148:Caspase 3; D018631:ras Proteins