Cell cycle arrest and differential gene expression in HT-29 cells exposed to an aqueous garlic extract.
Epidemiological data show an inverse correlation between garlic consumption and the risk for colon cancer. To examine this relationship, HT-29 human adenocarcinoma cells were cultured in the presence and absence of an aqueous garlic extract. Garlic treatment resulted in a fraction of cells detaching from the culture flasks. These cells remained viable. Flow cell cytometry showed that untreated cells exhibited a normal distribution among phases of the cell cycle, with 12% of cells at the G2/M boundary. Of the garlic-treated cells remaining attached to the flask, 27% were present at the G2/M boundary. Treated cells that detached from the flask were found almost exclusively (89%) at the G2/M boundary. RNA fingerprinting and microarray analysis showed that expression of the gene for menin was twice as high in control cells as in detached treated cells. In contrast, expression of genes for epidermal growth factor receptor and integrin-alpha6 was nearly twice as high in detached treated cells as in control cells. These changes in gene expression were consistent with an arrest of the cell cycle at the G2/M boundary. Garlic's arrest of the cell cycle in human adenocarcinoma cells may explain in part its anticarcinogenic properties.
Frantz
D J
DJ
Department of Food Science and Nutrition, Brigham Young University, Provo, UT 84602, USA.
Hughes
B G
BG
Nelson
D R
DR
Murray
B K
BK
Christensen
M J
MJ
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D016172:DNA Fingerprinting; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D005737:Garlic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014867:Water
C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014867:Water