Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro
Braz. j. med. biol. res
; 37(4): 591-599, Apr. 2004. tab, graf
Article
in English
| LILACS
| ID: lil-357109
Responsible library:
BR1.1
RESUMO
This paper describes the effect of dipyridamole (DIP) on the cytotoxicity of cisplatin in HEp-2 human larynx cancer cells in vitro and the nature of the interaction between cisplatin and dipyridamole. Cytotoxic assays were performed to obtain the IC50 for cisplatin. The cells were treated with 0, 20, 40, 80, 120 or 200 µM cisplatin, with or without a single concentration of DIP and incubated for 60 min at 37ºC and 5 percent CO2 for 3 days and then counted with a hemocytometer. The accumulation of cisplatin in the cells was measured by atomic absorption and fluorescence was used to determine the membrane binding constant of DIP. In the presence of 10, 20 and 30 µM DIP, the IC50 of cisplatin was reduced by 25, 60 and 82 percent in HEp-2 cells. Combination index analysis revealed that cisplatin and DIP interact synergistically. In larynx cancer cells, the accumulation of cisplatin increased by 13, 27 and 65 percent as the DIP concentration was increased from 10 to 20 and 30 µM, respectively. The binding constant of DIP to the cell membrane was estimated to be 0.36 ± 0.12 mg/ml (N = 2) by fluorescence and cisplatin did not suppress DIP fluorescence. These results suggest that DIP significantly enhances cisplatin cytotoxicity in HEp-2 cells by increasing cisplatin accumulation, probably by altering the cell membrane as suggested by its binding constant. The results obtained reinforce the importance of combination therapy to reduce the doses of chemotherapeutic drugs and therefore the side effects of chemotherapy.
Full text:
Available
Collection:
International databases
Health context:
SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases
Health problem:
Larynx Cancer
/
Other Respiratory Diseases
Database:
LILACS
Main subject:
Laryngeal Neoplasms
/
Cisplatin
/
Dipyridamole
/
Antineoplastic Agents
Limits:
Humans
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2004
Document type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade de São Paulo/BR