Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance

John S. Coon, Warren Knudson, Kathleen Clodfelter, Bing Lu, Ronald S Weinstein

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

A recently developed non-ionic surfactant called Solutol HS 15 (polyoxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells. At a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls), Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively. Solutol HS 15 was relatively much more potent than the prototypic reversing agent, verapamil, for reversing colchicine resistance, compared to the ability of each agent to reverse vinblastine resistance. Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific. Considering their different structure and different relative potency for reversing colchicine resistance, Solutol HS 15 and verapamil probably reverse multidrug resistance by different mechanisms. Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo.

Original languageEnglish (US)
Pages (from-to)897-902
Number of pages6
JournalCancer Research
Volume51
Issue number3
StatePublished - Feb 1 1991
Externally publishedYes

Fingerprint

Multiple Drug Resistance
Esters
Acids
Verapamil
Rhodamine 123
Colchicine
Vinblastine
Solutol HS 15
Active Biological Transport
Drug-Related Side Effects and Adverse Reactions
Surface-Active Agents
Alanine
Pharmaceutical Preparations
Doxorubicin
Inhibitory Concentration 50
Squamous Cell Carcinoma
Flow Cytometry
Glucose
Membranes
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance. / Coon, John S.; Knudson, Warren; Clodfelter, Kathleen; Lu, Bing; Weinstein, Ronald S.

In: Cancer Research, Vol. 51, No. 3, 01.02.1991, p. 897-902.

Research output: Contribution to journalArticle

Coon, John S. ; Knudson, Warren ; Clodfelter, Kathleen ; Lu, Bing ; Weinstein, Ronald S. / Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance. In: Cancer Research. 1991 ; Vol. 51, No. 3. pp. 897-902.
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