Takayoshi Matsui

Promoter activation and following induction of the p21/WAF1 gene by flavone is involved in G1 phase arrest in A549 lung adenocarcinoma cells

Flavonoids are present in many plants including edible fruits and vegetables. Recently, many of the biological activities of flavonoids have been elucidated. Flavone is a well known flavonoid, and many of its derivatives have been shown to have anti‐proliferative effects on several cancer cells. We report here that flavone can effectively inhibit the cell growth of human lung adenocarcinoma A549 cells in a dose‐dependent manner, and 100 μM flavone causes cell cycle arrest at the G1 phase. As a mechanism underlying the cell cycle arrest, flavone markedly increases the mRNA and protein levels of a universal inhibitor of cyclin‐dependent kinase, p21/WAF1, and inhibits phosphorylation of retinoblastoma (RB) protein. Although A549 cells possess wild‐type p53, flavone does not induce the p53 protein, suggesting that p21/WAF1 induction is p53‐independent. In addition, 100 μM flavone significantly increases the promoter activity of the p21/WAF1 gene by 5‐fold. These results suggest that the G1 phase arrest by flavone is due to p53‐independent transcriptional induction of the p21/WAF1 gene and the subsequent dephosphorylation of RB protein.

Effects of Quercetin and/or Restraint Stress on Formation of Aberrant Crypt Foci Induced by Azoxymethane in Rat Colons

The present study examines the effect of dietary quercetin and/or restraint stress on the formation of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in the colon. Female F344 rats were divided into four groups. All animals were given intraperitoneal injections of AOM. The animals were fed a basal diet (group A, C), or a 2% quercetin-supplemented diet (group B, D). The animals were put individually to narrow wire cages for 1 h every day throughout the study to expose them to mild restraint stress (group C, D). At week 5, all the rats were killed and analyzed for ACF in the colon. The number of ACF increased significantly in the animals subjected to stress (p < 0.05). On the other hand, dietary quercetin significantly reduced the number of ACF in both the nonstress (p < 0.001) and stress groups (p < 0.05). These findings suggest that quercetin might have a potential as a chemopreventive drug for colon cancer despite stress.

Ammonia Inhibits Proliferation and Cell Cycle Progression at S-Phase in Human Gastric Cells

Helicobacter pylori (Hp) has strong ureaseactivity and produces a large amount of ammonia in thestomach. In animal studies, ammonia was shown toaccelerate cell kinetics of gastric mucosa, andlong-term exposure of the stomach to ammonia leads tomucosal atrophy. To understand this process, we examinedthe effects of ammonia on the growth and cell cycleprogression of human gastric cancer cell lines (HGC-27, MKN1, MKN45) using flowcytometric analysis. Ineach cell line, ammonia inhibited the cell growth in adose-dependent manner and caused significantaccumulation of S-phase cells at a cytostatic dose. DNA synthesis of HGC-27 cells treated with ammoniawas also suppressed to about 50% of that of theuntreated cells. Similar effects were observed onaddition of ammonium chloride at the same concentration, while adjusting the pH of the media with NaOHalone to that with the cytostatic dose of ammonia didnot affect the cell cycle progression. Theseobservations indicate that ammonia induces S-phasearrest in gastric cells independently of pH.