Comparative anticancer effects of flavonoids and diazepam in cultured cancer cells.
This study examined the comparative anticancer effects of flavonoids and diazepam in the cultured cancer cells. In the SNU-C4 colorectal and MDA-MB-231 breast adenocarcinoma cells, apigenin and fisetin, flavonoids, and diazepam inhibited cancer cell survival concentration and incubation-time dependently. Diazepam consistently inhibited FAS activity, a known anticancer mechanism of flavonoids, in a concentration dependent manner. Unlike diazepam, in highly aggressive breast MDA-MB-231 cells known to have a nuclear/perinuclear located PBR, PK11195, a specific PBR ligand enhanced the proliferation of cells, and the proliferative effect of PK11195 was reversed by an addition of lovastatin, a HMG-CoA reductase inhibitor. Diazepam- and flavonoids-induced cytotoxic activity in both cancer cell lines was not reduced by the addition of 5-fluorouracil (5-FU), a chemotherapeutic agent. Like flavonoids, diazepam inhibited the release of vascular endothelial growth factor (VEGF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) into supernatants of cultured in the SNU-C4 and MDA-MB-231 cells. In conclusion, this study provided in vitro information on the safe use of sedative in oncologic patients.
Kim
Dae-Hyun
DH
Nuclear Medicine, School of Medicine, Kyungpook National University, Jung-Gu, Daegu, Republic of Korea.
Lee
Jae-Tae
JT
Lee
In-Kyu
IK
Ha
Jeoung-Hee
JH
D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D005472:Fluorouracil / Q000633:toxicity; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D054872:Fatty Acid Synthesis Inhibitors; D005419:Flavonoids; D044948:Flavonols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006993:Hypnotics and Sedatives; D007546:Isoquinolines; D042461:Vascular Endothelial Growth Factor A; D047310:Apigenin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008148:Lovastatin; D064429:Fatty Acid Synthases; C017875:fisetin; D003975:Diazepam; D005472:Fluorouracil; C037850:PK 11195