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. 2005 Aug 19;95(12):936–942. doi: 10.1111/j.1349-7006.2004.tb03180.x

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

Hiroyuki Ohnishi 1,2, Makoto Asamoto 1,✉, Kazunari Tujimura 1,3, Naomi Hokaiwado 1, Satoru Takahashi 1, Kumiko Ogawa 1, Masanori Kuribayashi 1,4, Tadashi Ogiso 1, Harumi Okuyama 2, Tomoyuki Shirai 1
PMCID: PMC11158043  PMID: 15596041

Abstract

Dietary phytochemicals can inhibit the development of certain types of tumors. We here investigated the effects of nobiletin (Nob), garcinol (Gar), auraptene (Aur), β‐cryptoxanthin‐ and hes‐peridine‐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.

AAbbreviations:

ACA

1,1′‐acetoxychavicol acetate

Aur

auraptene

CHRP

β‐cryptoxanthin‐ and hesperidine‐rich pulp

DEN

diethylnitrosamine

EC20

20% effective concentration

Gar

garcinol

GST‐P

glutathione S‐transferase placental form

HCC

hepatocellular carcinoma

HGF

hepatocyte growth factor

Nob

nobiletin

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