Reversal of doxorubicin resistance by hydrophobic, but not hydrophilic, forskolins

Scott Wadler, Chia-Ping H. Yang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The plant diterpene forskolin reverses acquired resistance to doxorubicin in variants of the murine sarcoma S180 cell line. Because forskolin is known to elevate intracellular cAMP levels, investigations were performed to determine whether this reversal of resistance resulted from effects on signal transduction. Two analogues of forskolin, dideoxyforskolin, which does not elevate cAMP, and a water-soluble analogue, were also investigated. Although all three diterpenes elevated levels of either cAMP or protein kinase C, these effects were not consistently associated with reversal of doxorubicin resistance. Likewise, all three diterpenes were capable of displacing [3H]azidopine from P-glycoprotein, but reversal of doxorubicin resistance was observed only with forskolin and dideoxyforskolin, suggesting that binding to P-glycoprotein may be a necessary, but not sufficient, condition for reversing doxorubicin resistance. The hydrophobicity of the compounds appeared to be the single factor most consistently related to reversal of doxorubicin resistance in this cell system, with the hydrophilic compound water-soluble forskolin failing to produce this result, even at concentrations 10-fold higher than effective concentrations of the hydrophobic diterpenes.

Original languageEnglish (US)
Pages (from-to)960-964
Number of pages5
JournalMolecular Pharmacology
Volume40
Issue number6
StatePublished - Dec 1991

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Colforsin
Doxorubicin
Diterpenes
P-Glycoprotein
Water
Hydrophobic and Hydrophilic Interactions
Sarcoma
Protein Kinase C
Signal Transduction
Cell Line

ASJC Scopus subject areas

  • Pharmacology

Cite this

Reversal of doxorubicin resistance by hydrophobic, but not hydrophilic, forskolins. / Wadler, Scott; Yang, Chia-Ping H.

In: Molecular Pharmacology, Vol. 40, No. 6, 12.1991, p. 960-964.

Research output: Contribution to journalArticle

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