Search

20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM-1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 μM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 μM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 μM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis.

Enhanced garlic (Allium sativum) consumption is closely related to reduced cancer incidence, as shown in epidemiological studies. Diallyl disulfide (DADS), a component of garlic, inhibits the proliferation of human blood, colon, lung and skin cancer cells. Although DADS had been reported to induce apoptosis in human leukemia HL-60 cells, there are no reports regarding whether or not it affects leukemia cells in vivo. Therefore, the present study is focused on the in vivo effects of DADS on WEHI-3 leukemia cells. The effects of DADS on murine WEHI-3 cells were initially examined, and the results indicated that DADS induced cytotoxicity and that this effect was dose-dependent. The effects of DADS on WEHI-3 in BALBIc mice were also examined, and the results indicated that DADS decreased the percentage of MAC-3 marker, indicating that differentiation of the precursor of macrophage and T cells was inhibited. The weights of liver and spleen were also measured, and the results indicated that DADS decreased the weight of these organs. An important characteristic of WEHI-3 leukemia is the enlarged spleen in mice after i.p. injection of WEHI-3 cells. Based on pathological examination, the function of DADS was observed in the liver and spleen of mice previously injected with WEHI-3 cells. Apparently, DADS affects WEHI-3 cells both in vitro and in vivo.