Adenylate cyclase toxin from Bordetella pertussis enhances cisplatin-induced apoptosis to lung cancer cells in vitro.
The present study examined the possibility to enhance lung cancer cell cytotoxicity and apoptosis of the anticancer drug cisplatin by exposure with adenylate cyclase (AC) toxin from Bordetella pertussis. A malignant mesothelioma cell line (P31) and a small-cell lung cancer cell line (U1690) were exposed to increasing concentrations of cisplatin and AC toxin, alone or in combination. Cytotoxicity was determined by a fluorescein-based assay and apoptosis by flow cytometry quantification of annexin V binding. Caspase-3, -8, and -9 activities were measured by enzyme activity assays. The cytotoxicity of AC toxin was time and dose dependent with an LD50 value at 72 h of 3 and 7 mg/L for P31 cells and U1690 cells, respectively. Cisplatin showed a similar time- and dose-dependent cytotoxicity, which was increased in the presence of a low toxic concentration (1 mg/L) of AC toxin. Furthermore, cisplatin caused a dose-dependent increase of annexin V binding cells of both cell lines after 24-h incubation, which was also enhanced in combination with AC toxin. AC toxin (1 mg/L) increased cisplatin-induced caspase-3, -8, and -9 activities in U1690 cells. Only minor increases of caspase-8 and -9 were noted for P31 cells. The present results, together with the knowledge that bacterial toxins decrease side effects of traditional cancer treatment, suggest a possibility to use them to enhance the therapeutic effect of cancer chemotherapy with reduced clinical adverse effects.
Department of Medical Biosciences, Clinical Chemistry, Umeå University, Sweden.
David
D
Johansson
Per
P
Bergström
Roger
R
Henriksson
Kjell
K
Grankvist
Anders
A
Johansson
Parviz
P
Behnam-Motlagh
D037361:Adenylate Cyclase Toxin / Q000378:metabolism* / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001886:Bordetella pertussis / Q000201:enzymology* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D007928:Lethal Dose 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology
D037361:Adenylate Cyclase Toxin; D000970:Antineoplastic Agents; D002945:Cisplatin