Doxorubicin induces apoptosis of cardiomyocytes: in vitro studies
| Cell Line | Treatment | Pathway Mechanism | Inhibitors/Survival Factors | Reference |
|---|---|---|---|---|
| H9c2 | DOX | Intrinsic (early mitochondrial dysfunction, cytochrome c release) | Green and Leeuwenburgh, 2002 | |
| DOX | Intrinsic (Bax upregulation, cytochrome c release) | Wang et al., 1998a | ||
| Wang et al., 1998b | ||||
| Neonatal rat cardiomyocytes | rFasL + DOX | Extrinsic | Yamaoka et al., 2000 | |
| DOX | Intrinsic | LIF-inhibits apoptosis via Bax phosphorylation/translocation | Negoro et al., 2001 | |
| DOX | Intrinsic | IGF-1 inhibits apoptosis via PI-3K/Akt activation and caspase 9 phosphorylation/inhibition | Wu et al., 2000 | |
| DOX | Intrinsic | JNK-c-JUN activation, ATF 3 expression, p53 downregulation | Nobori et al., 2002 | |
| Adult mouse cardiomyocytes | DOX | P38 MAPKs activation | Metallothioneins inhibit apoptosis | Kang et al., 2000 |
| DOX | Intrinsic (activation of acid sphingomyelinases, ceramide formation, coupling of voltage-independent B-type Ca2+ channels with the opening of transition pore) | l-Carnitine protects by inhibiting acid acid sphingomyelinase(s) | Andrieu-Abadie et al., 1999 | |
| Henaff et al., 2002 | ||||
| HL-1 or adult rat cardiomyocytes | DOX, DNR | Intrinsic (down-regulation of Bcl-XL) | Kim et al., 2003b | |
| Kitta et al., 2003 |
IGF-1, insulin growth factor-1; LIF, leukemia inhibiting factor; MAPK, p38 mitogen-activated protein kinases; PI-3K/Akt, phosphoinositide kinase-serine/threonine kinase; rFasL, recombinant Fas ligand.