Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity
Rephaeli, A; Waks-Yona, S; Nudelman, A; Tarasenko, I; Tarasenko, N; Phillips, DR; Cutts, SM; Kessler-Icekson, G
HERO ID
1454193
Reference Type
Journal Article
Year
2007
Language
English
PMID
| HERO ID | 1454193 |
|---|---|
| In Press | No |
| Year | 2007 |
| Title | Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity |
| Authors | Rephaeli, A; Waks-Yona, S; Nudelman, A; Tarasenko, I; Tarasenko, N; Phillips, DR; Cutts, SM; Kessler-Icekson, G |
| Journal | British Journal of Cancer |
| Volume | 96 |
| Issue | 11 |
| Page Numbers | 1667-1674 |
| Abstract | Formaldehyde has been previously shown to play a dominant role in promoting synergy between doxorubicin (Dox) and formaldehyde-releasing butyric acid (BA) prodrugs in killing cancer cells. In this work, we report that these prodrugs also protect neonatal rat cardiomyocytes and adult mice against toxicity elicited by Dox. In cardiomyocytes treated with Dox, the formaldehyde releasing prodrugs butyroyloxymethyl diethylphosphate (AN-7) and butyroyloxymethyl butyrate (AN-1), but not the corresponding acetaldehyde-releasing butyroyloxydiethyl phosphate (AN-88) or butyroyloxyethyl butyrate (AN-11), reduced lactate dehydrogenase leakage, prevented loss of mitochondrial membrane potential (DeltaPsim) and attenuated upregulation of the proapoptotic gene Bax. In Dox-treated mice, AN-7 but not AN-88 attenuated weight-loss and mortality, and increase in serum lactate dehydrogenase. These findings show that BA prodrugs that release formaldehyde and augment Dox anticancer activity also protect against Dox cardiotoxicity. Based on these observations, clinical applications of these prodrugs for patients treated with Dox warrant further investigation. |
| Doi | 10.1038/sj.bjc.6603781 |
| Pmid | 17473824 |
| Wosid | WOS:000246816200008 |
| Url | https://www.proquest.com/scholarly-journals/anticancer-prodrugs-butyric-acid-formaldehyde/docview/70550101/se-2 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000246816200008 |
| Is Public | Yes |
| Language Text | English |
| Keyword | doxorubicin; cardiomyocytes; formaldehyde; prodrugs; histone acetylation |