Mitochondria-targeted antioxidant SkQR1 selectively protects MDR (Pgp 170)-negative cells against oxidative stress

FEBS Lett. 2010 Feb 5;584(3):562-6. doi: 10.1016/j.febslet.2009.12.002. Epub 2009 Dec 6.

Abstract

A conjugate of plastoquinone with decylrhodamine 19 (SkQR1) selectively accumulates in mitochondria of normal and tumor cells. SkQR1 protected the cellular pool of reduced glutathione under oxidative stress. Overexpression of P-glycoprotein (Pgp 170) multidrug resistance pump strongly suppresses accumulation of SkQR1. The inhibitors of Pgp 170 stimulate accumulation of SkQR1 in various cell lines indicating that SkQR1 is a substrate of Pgp 170. The protective effect of SkQR1 against oxidative stress is diminished in the cells overexpressing Pgp 170. It is suggested that mitochondria-targeted antioxidants could selectively protect normal (Pgp 170-negative) cells against the toxic effect of anti-cancer treatments related to oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Antioxidants / metabolism*
  • Antioxidants / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Oxidative Stress / drug effects*
  • Plastoquinone / analogs & derivatives*
  • Plastoquinone / metabolism
  • Plastoquinone / pharmacology
  • Rhodamines / metabolism*
  • Rhodamines / pharmacology*

Substances

  • 10-(6'-plastoquinonyl) decylrhodamine 19
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antioxidants
  • Rhodamines
  • Plastoquinone