Vitamin E reverses multidrug resistance in vitro and in vivo

Cancer Lett. 2013 Aug 9;336(1):149-57. doi: 10.1016/j.canlet.2013.04.020. Epub 2013 Apr 23.

Abstract

Multidrug resistance (MDR) is a major obstacle to successful and effective chemotherapeutic treatments of cancers. This study explored the reversal effects of vitamin E on MDR tumor cells in vitro and in vivo, elucidating the potential mechanism of this reversal. VE at a concentration of 50 μM exhibited a significant reversal of the MDR effect (compared to only PTX in DMSO, p<0.05) in two human MDR cell lines (H460/taxR and KB-8-5). The MDR cell xenograft model was established to investigate the effect of VE on reversing MDR in vivo. Mice intravenously injected with Taxol (10 mg/kg) with VE (500 mg/kg, IP) showed an ability to overcome the MDR. VE and its derivatives can significantly increase intracellular accumulation of rhodamine 123 and doxorubicin (P-gp substrate), but not alter the levels of P-gp expression. These treatments also did not decrease the levels of intracellular ATP, but were still able to inhibit the verapamil-induced ATPase activity of P-gp. The new application of VE as an MDR sensitizer will be attractive due to the safety of this treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adenosine Triphosphate / chemistry
  • Animals
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Paclitaxel / pharmacology
  • Time Factors
  • Vitamin E / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antioxidants
  • Vitamin E
  • Adenosine Triphosphate
  • Paclitaxel