Antineoplastic and cytogenetic effects of chlorpromazine on human lymphocytes in vitro and on Ehrlich ascites tumor cells in vivo.
The inhibitory effect of phenothiazines in tumor growth and cancer cell proliferation in vitro and in vivo has been established. These reports motivated us to investigate the genotoxic, cytotoxic, and cytostatic potential of chlorpromazine, alone or in combination with mitomycin C, in vitro and in vivo. Sister chromatid exchange levels were assessed providing a quantitative index of genotoxicity. In-vitro studies were performed on human lymphocyte cultures and in-vivo studies involved Ehrilch ascites tumor (EAT) cells. An antitumour study was also conducted on the survival time and the ascitic volume in EAT-bearing Balb/C mice. The combination of chlorpromazine plus caffeine and mitomycin C exerted cytostatic and cytotoxic actions in human lymphocytes. The combination of chlorpromazine plus mitomycin C exerted cytostatic and cytotoxic actions in EAT cells, significantly increased the survival span of the mice inoculated with EAT cells, and suppressed the expected tumor growth increase. The findings of this basic study illustrate that high chlorpromazine concentrations increase chemotherapeutic effectiveness of mitomycin C. Chlorpromazine concentrations within the observed human plasma concentration range need to be tested along with antineoplastic agents in vitro for its synergistic action so as to evaluate a potential clinical application. Further investigation including other phenothiazines, biological systems, and cancer models is required.
Lialiaris
Theodore S
TS
Department of Genetics, Laboratory of Genetics, Medical School, Demokritos University of Thrace, University Campus-Dragana, Alexandroupolis 681 00, Greece. lialiari@med.duth.gr
Papachristou
Fotini
F
Mourelatos
Constantine
C
Simopoulou
Maria
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002110:Caffeine / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology* / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000494:pharmacology / Q000627:therapeutic use; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D002110:Caffeine; D016685:Mitomycin; D002746:Chlorpromazine