Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication.
Fucoxanthin is one of the most abundant carotenoids found in Undaria pinnatifida and has been shown to inhibit tumor proliferation in vitro. However, the mechanisms underlying the anti-cancer effects of fucoxanthin are unclear. In this study, we hypothesized that fucoxanthin may cause cell cycle arrest and enhance gap junctional intercellular communication (GJIC) in SK-Hep-1 human hepatoma cells. Data revealed that fucoxanthin (1-20microM) strongly and concentration-dependently inhibited the proliferation of SK-Hep-1 cells at 24h of incubation, whereas fucoxanthin facilitated the growth of a murine embryonic hepatic (BNL CL.2) cells at 24h of incubation and only slightly slowed the cell proliferation at 48h. In SK-Hep-1 cells, fucoxanthin caused cell cycle arrest at G0/G1 phase and induced cell apoptosis, as evidenced by increased subG1 cells and induction of DNA strand breaks. Using scrape loading-dye-transfer assay, fucoxanthin was found to significantly enhance GJIC of SK-Hep-1 cells without affecting that of BNL CL.2 cells. In addition, fucoxanthin significantly increased protein and mRNA expressions of connexin 43 (Cx43) and connexin 32 (Cx32) in SK-Hep-1 cells. Moreover, fucoxanthin markedly increased the concentration of intracellular calcium levels in SK-Hep-1 cells. Thus, fucoxanthin is specifically antiproliferative against SK-Hep-1 cells, and the effect is associated with upregulation of Cx32 and Cx43, which enhances GJIC of SK-Hep-1 cells. The enhanced GJIC may be responsible for the increase of the intracellular calcium level, which then causes cell cycle arrest and apoptosis.
Liu
Cheng-Ling
CL
Department of Food Science, National Chung-Hsing University, 250 Kuo-Kuang Road, Taichung, 402, Taiwan.
Huang
Yung-Sheng
YS
Hosokawa
Masashi
M
Miyashita
Kazuo
K
Hu
Miao-Lin
ML
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002450:Cell Communication / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy*; D051189:Murinae; D012333:RNA, Messenger / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D024341:Xanthophylls / Q000494:pharmacology* / Q000627:therapeutic use; D000097002:Gap Junction beta-1 Protein
D016588:Anticarcinogenic Agents; D002118:Calcium; D018031:Connexin 43; D017630:Connexins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D024341:Xanthophylls; D000097002:Gap Junction beta-1 Protein; C025164:fucoxanthin