title: Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: comparison with osteosarcoma cells.
abstract: OBJECTIVE
  Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells.
  
  
  METHODS
  This study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1 mg/kg, thrice weekly) and high (3 mg/kg thrice weekly) dose Dox for a month.
  
  
  RESULTS
  There was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100 nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed ∼ 40% reduction in cell viability after 24 h.
  
  
  CONCLUSIONS
  In culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo.
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Oktay
authors.initials: O
authors.lastname: Tacar
authors.forename: Sivanjah
authors.initials: S
authors.lastname: Indumathy
authors.forename: Mei Lin
authors.initials: ML
authors.lastname: Tan
authors.forename: Swati
authors.initials: S
authors.lastname: Baindur-Hudson
authors.forename: Anna M
authors.initials: AM
authors.lastname: Friedhuber
authors.forename: Crispin R
authors.initials: CR
authors.lastname: Dass
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D012867:Skin / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin
keywords: Bax; Beclin-1; apoptosis; autophagy; cardiotoxicity