Microtubule-targeted agents: when mitochondria become essential to chemotherapy

Biochim Biophys Acta. 2011 Jun;1807(6):679-88. doi: 10.1016/j.bbabio.2011.01.001. Epub 2011 Jan 7.

Abstract

Microtubule-Targeting Agents (MTAs) constitute a class of drugs largely used for cancer treatment in adults and children. In cancer cells, they suppress microtubule dynamics, and induce cell death via the mitochondrial intrinsic pathway. To date, links between mitochondria and microtubule network disturbance in MTAs mechanism of action are not obvious. The aim of the present contribution is to provide elements that could answer to the question: how far are mitochondria essential to anticancer chemotherapy that targets the microtubule cytoskeleton? We review the main molecular candidates to link microtubule alteration with the apoptotic mitochondrial pathway control. Involvement of direct targeting of mitochondria in MTA efficacy is also discussed. Furthermore, we line up current evidence and emerging concepts on the participation of both mitochondria and microtubule in MTA neurotoxic side effects. To decipher the interconnections between the mitochondrial and the microtubule networks may help to improve cancer cell response to chemotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Humans
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Treatment Outcome
  • Tubulin Modulators / administration & dosage
  • Tubulin Modulators / pharmacology
  • Tubulin Modulators / therapeutic use*

Substances

  • Tubulin Modulators