ORIGINAL ARTICLESResearch on the anti-tumour effect of steroid lactam alkylator (NSC-294859) in comparison with conventional chemotherapeutics in malignant melanomaTrafalis, Dimitrios T.P.a b; Camoutsis, Charalambosa; Papageorgiou, AthanasioscAuthor Information aLaboratory of Pharmaceutical Chemistry, School of Pharmacy, University of Patras bFirst Department of Medical Oncology, ‘METAXA’ Cancer Hospital, Piraeus cLaboratory of Experimental Chemotherapy, Theagenion Anticancer Institute, Thessaloniki, Greece Correspondence and requests for reprints to Dr Dimitrios Trafalis, 15 Larnakos, 17341 Agios Dimitrios, Athens, Greece Tel: +30 210 971 5465; fax: +30 210 971 3766; e-mail: [email protected]/[email protected] Received 2 September 2004 Accepted (after revision) 8 March 2005 Melanoma Research: August 2005 - Volume 15 - Issue 4 - p 273-281 Buy Abstract Evidence indicating that hybrid steroid compounds of anti-cancer agents produce reduced toxicity, significantly lower than the cytotoxic components alone, and increased anti-cancer activity has prompted the design and development of such steroids, mostly alkylating esters. We investigated the in-vitro and in-vivo activity of a homo-aza-steroidal alkylating ester (HASE), in comparison with dacarbazine (DTIC), cisplatin (CPDD), carmustine (BCNU) and semustine (MeCCNU), in the treatment of malignant melanoma. Cytotoxicity was assessed in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using a panel of six human malignant melanoma cell lines, with or without the presence of rat liver microsome assay. B16 melanoma-bearing mice were used to evaluate in vivo the anti-tumour activity of the tested compounds. In all cases of in-vitro screening, HASE displayed a significantly higher (P<0.0001) cytostatic and cytotoxic effect than DTIC, BCNU and MeCCNU, but produced significantly lower (P<0.0001) activity than CPDD. HASE exhibited a significantly smaller range than CPDD between concentration levels that produced growth arrest and those that induced a cytotoxic effect against melanoma cells in vitro. The anti-tumour activity of HASE in B16 melanoma-bearing mice, as determined by tumour growth rate inhibition (<42%) and percentage survival prolongation (treated versus control, 167%), was significantly superior (P<0.001) to that achieved by DTIC, BCNU and MeCCNU and was equal to that of CPDD. HASE exhibited a toxicity similar to that of DTIC, BCNU and MeCCNU, but significantly lower than that of CPDD. It can be concluded that HASE displays significant in-vitro and in-vivo activity in the treatment of melanoma. © 2005 Lippincott Williams & Wilkins, Inc.