title: In vitro antiproliferative characteristics of flavonoids and diazepam on SNU-C4 colorectal adenocarcinoma cells.
abstract: The need for beneficial use of sedatives in oncologic patients is increasing. Therefore, in this study, antiproliferative characteristics of herbal and synthetic sedatives were examined in vitro in SNU-C4 human colorectal adenocarcinoma cells. Apigenin (50% inhibition concentration, IC(50) = 1.8 +/- 0.5 microM) and diazepam (IC(50) = 7.0 +/- 0.5 microM) showed concentration-dependent inhibition of SNU-C4 cancer cell survival. Efficacy of cancer cell survival inhibition by apigenin and diazepam was much lower than that of 5-fluorouracil (5-FU), a known chemotherapeutic drug. However, 10(-6) M concentration of apigenin and diazepam potentiated 5-FU-induced cytotoxicity. In SNU-C4 cells, 10(-6) M concentrations of diazepam, flumazenil (Ro15-1788), Ro5-4864, or PK11195, all ligands for central- or peripheral-type benzodiazepine (BZD) receptors, inhibited cell survival like the flavonoid apigenin (4',5,7-trihydroxyflavone) and fisetin (3,7,3',4'-tetrahydroxyflavone). Also like the plant flavonoids, treatment with 10(-6) M concentration of diazepam for 3 days hardly affect the peripheral-type BZD receptor (PBR) messenger RNA (mRNA) expression and inhibited glucose utilization of SNU-C4 cells. Treatment with flavonoids or diazepam for 6 days upregulated PBR mRNA expression and cell cytotoxicity of SNU-C4 cells. Furthermore, treatment with 10(-6) M concentration of apigenin, a natural sedative material originating from traditional herbs, positively modulated BZD-induced antiproliferative cytotoxicity in SNU-C4 cells. Overall, the in vitro antiproliferative activity on SNU-C4 cancer cells of herbal sedatives, such as apigenin, plus additive enhancement of synthetic BZD- and 5-FU-induced antiproliferative activities, were shown. In conclusion, this study provides experimental basis for advanced trial in the future.
authors.affiliation: Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 101 Dongin 2-Ga, Jung-Gu, Daegu, Republic of Korea.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Jae-Tae
authors.initials: JT
authors.lastname: Lee
authors.forename: Maan-Gee
authors.initials: MG
authors.lastname: Lee
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Sohn Joo
authors.initials: SJ
authors.lastname: Ahn
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: You La
authors.initials: YL
authors.lastname: Lee
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
authors.forename: Jeoung-Hee
authors.initials: JH
authors.lastname: Ha
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D047310:Apigenin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003975:Diazepam / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005419:Flavonoids / Q000008:administration & dosage; D044948:Flavonols; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044948:Flavonols; D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; D047310:Apigenin; C017875:fisetin; D003975:Diazepam; D005472:Fluorouracil