Doxorubicin-induced death in tumour cells and cardiomyocytes: is autophagy the key to improving future clinical outcomes?

J Pharm Pharmacol. 2013 Nov;65(11):1577-89. doi: 10.1111/jphp.12144. Epub 2013 Sep 18.


Objectives: Doxorubicin, a commonly used frontline chemotherapeutic agent for cancer, is not without side-effects. The original thinking that the drug causes necrosis in tumours has largely given way to its link with apoptosis over the past two decades.

Key findings: More recently, major biomarkers such as AMPK, p53 and Bcl-2 have been identified as important to apoptosis induction by doxorubicin. It is Bcl-2 and its interaction with Beclin-1 that has refocussed research attention on doxorubicin, albeit this time for its ability to induce autophagy. Autophagy can be either anticancerous or procancerous however, so it is critical that the reasons for which cancer cells undergo this type of cell biological event be clearly identified for future exploitation.

Summary: Taking a step back from treating patients with large doses of doxorubicin, which causes toxicity to the heart amongst other organs, and further research with this drug's molecular signalling in not only neoplastic but normal cells, may indeed redefine the way doxorubicin is used clinically and potentially lead to better neoplastic disease management.

Keywords: autophagy; cancer; cardiotoxicity; cell death; doxorubicin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1
  • Doxorubicin / adverse effects
  • Doxorubicin / pharmacology*
  • Doxorubicin / therapeutic use
  • Humans
  • Membrane Proteins / metabolism
  • Myocytes, Cardiac / drug effects*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism


  • Antibiotics, Antineoplastic
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Doxorubicin