Second stage tumor promoters: Differences in biological potency and phorbol ester receptor affinity in C6 cells

Karen L. Leach; Mitchell M. Frost; Peter M. Blumberg; Joseph P. Bressler

doi:10.1016/0304-3835(87)90085-1

Second stage tumor promoters: Differences in biological potency and phorbol ester receptor affinity in C6 cells

Karen L. Leach, Mitchell M. Frost, Peter M. Blumberg, Joseph P. Bressler

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

We have shown that the second stage tumor promoters mezerein (MEZ) and phorbol 12-retinoate 13-acetate (PRA) inhibit the glucocorticoid-induced increase in glycerol phosphate dehydrogenase (GPDH) activity in C6 rat glioma cells with ED₅₀-values of 3.9 and 2.9 nM, respectively. Phorbol 12-myristate 13-acetate (PMA) was 10-fold less potent. MEZ was likewise more potent than PMA for inhibition of cAMP formation in response to isoproterenol. Binding competition studies using [³H]phorbol 12,13-dibutyrate ([³H]PDBu) yielded apparent K_i-values for MEZ and PRA of 50-70 nM. The large difference between the biological potencies of MEZ and PRA and their affinity for the major phorbol ester receptor suggest they may be acting through a more complicated mechanism in these cells.

Original language	English (US)
Pages (from-to)	139-147
Number of pages	9
Journal	Cancer Letters
Volume	36
Issue number	2
DOIs	https://doi.org/10.1016/0304-3835(87)90085-1
State	Published - Aug 1987
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "Second stage tumor promoters: Differences in biological potency and phorbol ester receptor affinity in C6 cells",

abstract = "We have shown that the second stage tumor promoters mezerein (MEZ) and phorbol 12-retinoate 13-acetate (PRA) inhibit the glucocorticoid-induced increase in glycerol phosphate dehydrogenase (GPDH) activity in C6 rat glioma cells with ED50-values of 3.9 and 2.9 nM, respectively. Phorbol 12-myristate 13-acetate (PMA) was 10-fold less potent. MEZ was likewise more potent than PMA for inhibition of cAMP formation in response to isoproterenol. Binding competition studies using [3H]phorbol 12,13-dibutyrate ([3H]PDBu) yielded apparent Ki-values for MEZ and PRA of 50-70 nM. The large difference between the biological potencies of MEZ and PRA and their affinity for the major phorbol ester receptor suggest they may be acting through a more complicated mechanism in these cells.",

author = "Leach, {Karen L.} and Frost, {Mitchell M.} and Blumberg, {Peter M.} and Bressler, {Joseph P.}",

year = "1987",

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T1 - Second stage tumor promoters

T2 - Differences in biological potency and phorbol ester receptor affinity in C6 cells

AU - Leach, Karen L.

AU - Frost, Mitchell M.

AU - Blumberg, Peter M.

AU - Bressler, Joseph P.

PY - 1987/8

Y1 - 1987/8

N2 - We have shown that the second stage tumor promoters mezerein (MEZ) and phorbol 12-retinoate 13-acetate (PRA) inhibit the glucocorticoid-induced increase in glycerol phosphate dehydrogenase (GPDH) activity in C6 rat glioma cells with ED50-values of 3.9 and 2.9 nM, respectively. Phorbol 12-myristate 13-acetate (PMA) was 10-fold less potent. MEZ was likewise more potent than PMA for inhibition of cAMP formation in response to isoproterenol. Binding competition studies using [3H]phorbol 12,13-dibutyrate ([3H]PDBu) yielded apparent Ki-values for MEZ and PRA of 50-70 nM. The large difference between the biological potencies of MEZ and PRA and their affinity for the major phorbol ester receptor suggest they may be acting through a more complicated mechanism in these cells.

AB - We have shown that the second stage tumor promoters mezerein (MEZ) and phorbol 12-retinoate 13-acetate (PRA) inhibit the glucocorticoid-induced increase in glycerol phosphate dehydrogenase (GPDH) activity in C6 rat glioma cells with ED50-values of 3.9 and 2.9 nM, respectively. Phorbol 12-myristate 13-acetate (PMA) was 10-fold less potent. MEZ was likewise more potent than PMA for inhibition of cAMP formation in response to isoproterenol. Binding competition studies using [3H]phorbol 12,13-dibutyrate ([3H]PDBu) yielded apparent Ki-values for MEZ and PRA of 50-70 nM. The large difference between the biological potencies of MEZ and PRA and their affinity for the major phorbol ester receptor suggest they may be acting through a more complicated mechanism in these cells.

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Second stage tumor promoters: Differences in biological potency and phorbol ester receptor affinity in C6 cells

Abstract

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