Effects of anticancer drugs, metals and antioxidants on cytotoxic activityof benzothiepins/benzoxepins

Among II benzothiepins/benzoxepins, 4-chloro-3,4-dihydro-2-(2-oxo-2-phenyle thyl)-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-a cetyl-L-cysteine and sodium ascorbate significantly reduced the cytotoxic a ctivity of [I] but not that of [2]. Compound [I] induced internucleosomol D NA fragmentation in human promyelocytic leukemic HL-60 cell line, but produ ced large DNA fragmentation in human oral tumor cell lines (HSC-2 MSG). Com pounds [I] and doxorubicin additively reduced the viable cell number of HSC -2 cells. These data, taken together with their tumor specific action, demo nstrate for the first time, the medicinal efficacy of benzothiepins/benzoxe pins.