(1-2-bis(1-2-benzisoselenazolone-3(2h)-ketone))ethane and Body-Weight

Ethaselen (1, 2-[bis (1, 2-Benzisoselenazolone-3 (2H) -ketone)] ethane, BBSKE), as a novel organoselenium compound targeting thioredoxin reductase (TrxR), has been reported to inhibit tumor growth and TrxR activity in several human tumor cell lines. It has now entered Phase I clinical trails. Here we report the effects of ethaselen and cisplatin (cis-diamminedichloroplatinum II, DDP) combination therapy (ethaselen 36 mg/kg, i.g., o.d. x 10 d and cisplatin 1 mg/kg, i.p., single at day 0) on human A549-grafted nude mouse model (female, BALB/c nude mouse, n = 5, treatment after tumor volume reached 100 mm(3)). Compared to single drug administration (either ethaselen: 36 mg/kg, i.g., o.d. x 10 d or cisplatin: 1.0 mg/kg, i.p., single at day 0), the combination therapy showed significantly reduced tumor size (presumably due to a synergistic effect) and no obvious toxic damage (both in terms of body weight maintenance and liver/kidney damage). These results will be significant in the development of novel anti-tumoral therapeutic strategies directed to non-small cell lung cancer (NSCLC).

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cisplatin; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Inhibitors; Female; Glutathione Peroxidase; Humans; Kidney; Kidney Function Tests; Lipid Peroxidation; Liver; Liver Function Tests; Mice; Mice, Nude; Organoselenium Compounds; Thioredoxin-Disulfide Reductase; Xenograft Model Antitumor Assays