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.