title: Effects of anticancer drugs, metals and antioxidants on cytotoxic activity of benzothiepins/benzoxepins.
abstract: Among 11 benzothiepins/benzoxepins, 4-chloro-3,4-dihydro-2-(2-oxo-2-phenylethyl)-1-benzothiepin-5-(2H)-one [1] showed the highest cytotoxicity against human oral squamous cell carcinoma HSC-2 cells, followed by 2,3-dihydro-2-(2-oxopropyl)-2-phenyl-1-benzoxepin [2]. Popular antioxidants, such as N-acetyl-L-cysteine and sodium ascorbate significantly reduced the cytotoxic activity of [1] but not that of [2]. Compound [1] induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cell line, but produced large DNA fragmentation in human oral tumor cell lines (HSC-2, HSG). Compounds [1] and doxorubicin additively reduced the viable cell number of HSC-2 cells. These data, taken together with their tumor specific action, demonstrate for the first time, the medicinal efficacy of benzothiepins/benzoxepins.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Terasawa
authors.forename: H
authors.initials: H
authors.lastname: Hosoya
authors.forename: Y
authors.initials: Y
authors.lastname: Sugita
authors.forename: I
authors.initials: I
authors.lastname: Yokoe
authors.forename: H
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001582:Benzothiepins / Q000737:chemistry / Q000494:pharmacology*; D001584:Benzoxepins / Q000737:chemistry / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D002470:Cell Survival / Q000187:drug effects; D003300:Copper; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005290:Ferric Compounds; D018922:HL-60 Cells; D006801:Humans; D008670:Metals; D015394:Molecular Structure; D009062:Mouth Neoplasms; D012468:Salivary Gland Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001582:Benzothiepins; D001584:Benzoxepins; D005290:Ferric Compounds; D008670:Metals; D003300:Copper; D004317:Doxorubicin