Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced cardiotoxicity in H9c2 myoblast cell line.
To investigate potential prevention or attenuation of anti- cancer drug induced cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be cytotoxic for the H9c2 cell line with IC50 of 30.69 ± 6.20 and 20.94 ± 6.05 mmol L-1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC50 could not be calculated. When 100 mmol L-1 doxorubicin was incubated for 72 hours with 50 mmol L-1 diltiazem, 100 mmol L-1 dexrazoxane and 100 mmol L-1 losartan, respectively, there was a 58.7 ± 10.2, 52.2 ± 11.7 and 44.7 ± 5.4 % reduction in cell death. When 200 mmol L-1 irinotecan was incubated for 72 hours with 100 mmol L-1 dexrazoxane, losartan and diltiazem, respectively, a 27.7 ± 6.9, 25.6 ± 5.1, and 19.1 ± 2.3 % reduction in cell death was observed. Our data suggests that losartan and diltiazem were as effective as dexrazoxane in protecting the cells against irinotecan- and doxorubicin-induced cell toxicity. These findings offer potential uses of anti- -ischemic drugs for ablation of cytotoxicity in response to mitochondrial injury, thereby improving patient outcomes and reducing health-care costs.
Tiam
T
Feridooni
Chris
C
Mac Donald
Di
D
Shao
Pollen
P
Yeung
Remigius U
RU
Agu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D002317:Cardiovascular Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D064730:Dexrazoxane / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D019808:Losartan / Q000494:pharmacology; D032446:Myoblasts / Q000187:drug effects* / Q000473:pathology; D051381:Rats
D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D064730:Dexrazoxane; D000077146:Irinotecan; D004317:Doxorubicin; D004110:Diltiazem; D019808:Losartan; D002166:Camptothecin