Article

Rerouting chlorambucil to mitochondria combats drug deactivation and resistance in cancer cells.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, ON M5S1A8, Canada.
Chemistry & biology (impact factor: 6.52). 04/2011; 18(4):445-53. DOI:10.1016/j.chembiol.2011.02.010 pp.445-53
Source: PubMed

ABSTRACT The difficulty of accessing the mitochondrial matrix has limited the targeting of therapeutics to this organelle. Here, we report, to our knowledge, the first successful delivery of an active DNA alkylating agent--chlorambucil--to mitochondria, and describe unexpected features that result from rerouting this drug within the cell. Mitochondrial targeting of this agent dramatically potentiates its activity, and promotes apoptotic cell death in a variety of cancer cell lines and patient samples. This retention of activity is observed even in cells with resistance to chlorambucil or disabled apoptotic triggering.

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Keywords

cancer cell lines
 
disabled apoptotic
 
first successful delivery
 
mitochondrial matrix
 
organelle
 
patient samples
 
promotes apoptotic cell death
 
unexpected features
 

Sonali B Fonseca