Interaction of forskolin with the P-glycoprotein multidrug transporter

Journal Article · Tue Aug 27 00:00:00 EDT 1991 · Biochemistry; (United States)

OSTI ID:5821973

Ming s, D I; Seamon, K B ^[1]; Speicher, L A; Tew, K D ^[2]; Ruoho, A E ^[3]

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1. Food and Drug Administration, Bethesda, MD (United States)
2. Fox Chase Cancer Research Center, Philadelphia, PA (United States)
3. Univ. of Wisconsin, Madison (United States)

Forskolin and 1,9-dideoxyforskolin, an analogue that does not activate adenylyl cyclase, were tested for their ability to enhance the cytotoxic effects of adriamycin in human ovarian carcinoma cells, SKOV3, which are sensitive to adriamycin and express low levels of P-glycoprotein, and a variant cell line, SKVLB, which overexpresses the P-glycoprotein and has the multidrug reing ance (MDR) phenotype. Forskolin and 1,9-dideoxyforskolin both increased the cytotoxic effects of adriamycin in SKVLB cells, yet had no effect on SKOV3 cells. Two photoactive derivatives of forskolin have been synthesized, 7-O-((2-(3-(4-azido-3-({sup 125}I)iodophenyl)propionamido)ethyl)carbamyl)forskolin, {sup 125}I-6-AIPP-Fsk, and 6-O-((2-(3-(4-azido-3-({sup 125}I)iodophenyl)propionamido)ethyl)carbamyl)forskolin, {sup 125}I-6-AIPP-Fsk, which exhibit specificity for labeling the glucose transporter and aing lyl cyclase, respectively. Both photolabels identified a 140-kDa protein in membranes from SKVLB cells whose labeling was inhibited by forskolin and 1,9-dideoxyforskolin. The data are consistent with forskolin binding to the P-glycoprotein analogous to that of other chemosensitizing drugs that have been shown to partially reverse MDR. The ability of forskolin photolabels to specifically label the transporter, the adenylyl cyclase, and the P-glycoprotein suggests that these proteins may share a common biing g domain for forskolin analogues.

• OSTI ID: 5821973
• Journal Information: Biochemistry; (United States), Vol. 30:34; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DRUGS
BIOLOGICAL EFFECTS
MEMBRANE PROTEINS
CROSS-LINKING
TERPENES
RADIORECEPTOR ASSAY
GLYCOPROTEINS
IODINE 125
BETA DECAY RADIOISOTOPES
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
POLYMERIZATION
PROTEINS
RADIOISOTOPES
TRACER TECHNIQUES
550200* - Biochemistry