Quercetin inhibits growth of COL0320 DM cells, derived from a human colon cancer. The inhibitory effect is partially reversible when quercetin is removed from the culture medium. Flow cytometric analysis has revealed that quercetin causes perturbation of the cell cycle, inducing a frozen cellcycle pattern and a block at the GI/S boundary. The synthesis of a 17-kDa protein was specifically inhibited by the addition of quercetin, and recovered when the cells at the G,/S boundary progressed into S-phase after the removal of quercetin from the culture medium. Furthermore, using synchronized cells obtained by centrifugal elutriation, we have shown that the rate of synthesis of a 17-kDa protein was low in GI, and high in S-phase of the cell cycle. Thus, this protein appears to be cell-cycle-related.
Quercetin (3,3',4',5,7-pentahydroxy flavone) is one of the most widely distributed bioflavonoids in the plant kingdom, and is a component of most edible fruits and vegetables (Kuhnau, 1976), each human consuming about 1 g of flavonoid per day in the diet. Quercetin is hardly absorbed by rats and passes through the gastrointestinal tract to be degraded by the intestinal microflora (Ueno et al., 1982). Although quercetin is a mutagen (Bjeldanes and Chang, 1977), experiments have proven its lack of carcinogenicity in vivo (Ambrose et al., 1951;Hirono et al., 1981). Quercetin also suppresses the promoting stage of carcinogenesis (Kato et al., 1983; Nishino et al., 1984). Therefore, it is of interest to investigate the effect of quercetin on gastrointestinal tumors which ordinarily enter into contact with food flavonoids. In this context, we examined the effect of quercetin on the human colon cancer cell line COL0320 DM (Quinn et al., 1979), and found that quercetin delays cell proliferation and causes suppression of the synthesis of a 17-kDa protein. We now present evidence suggesting that this 17-kDa protein is cell-cycle-related.
MATERIAL AND METHODS
Reagents
[6-3H]Thymidine (37.0 MBq/ml), L-[4,5-3H]leucine (37.0