Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo.
Dietary phytochemicals can inhibit the development of certain types of tumors. We here investigated the effects of nobiletin (Nob), garcinol (Gar), auraptene (Aur), beta-cryptoxanthin- and hesperidine-rich pulp (CHRP) and 1,1'-acetoxychavicol acetate (ACA) on hepatocarcinogenesis in a rat medium-term liver bioassay, and also examined their influence on cell proliferation, cell cycle kinetics, apoptosis and cell invasion of rat and human hepatocellular carcinoma (HCC) cells, MH1C1 and HepG2, respectively. While there were no obvious suppressive effects on the development of putative preneoplastic liver lesions, inhibition of hepatocarcinoma cell proliferation was evident in the Nob group. Nob also caused G2/M cell cycle arrest and apoptosis. Microarray analysis identified a set of genes specifically regulated by Nob, and these are likely to be involved in the observed growth suppression of HCC cells. These results suggest that phytochemicals might have chemopreventive potential in late stages of hepatocarcinogenesis.
Ohnishi
Hiroyuki
H
Department of Experimental Pathology and Tumor Biology, Nagoya City University, Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Asamoto
Makoto
M
Tujimura
Kazunari
K
Hokaiwado
Naomi
N
Takahashi
Satoru
S
Ogawa
Kumiko
K
Kuribayashi
Masanori
M
Ogiso
Tadashi
T
Okuyama
Harumi
H
Shirai
Tomoyuki
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019587:Dietary Supplements; D047309:Flavones / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000975:Antioxidants; D047309:Flavones; C008661:nobiletin