Response of rat and human prostatic cancers to the novel 5α-reductase inhibitor, SK and F 105657

J. C. Lamb, John Tod Isaacs, R. K. Johnson, J. T. Isaacs

Research output: Contribution to journalArticle

Abstract

The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R-3327 H and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5α-reductase inhibitor, SK and F 105657, was tested in vivo. SK and F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor and the human PC-82 tumor have a low to undetectable level of tissue 5α-reductase activity and both responded to SK and F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., >70%) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat R-3327 H prostatic cancer has a much higher level of tissue 5α-reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK and F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R- 3327 G tumor-bearing rats which experienced an antitumor response. These results suggest that SK and F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5α-reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5α-reductase activity could be treated with SK and F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5α-reductase activity.

Original languageEnglish (US)
Pages (from-to)15-34
Number of pages20
JournalProstate
Volume21
Issue number1
StatePublished - 1992

Fingerprint

Prostatic Neoplasms
Oxidoreductases
Dihydrotestosterone
Neoplasms
Androgens
Prostate
epristeride
Castration
Growth
Weights and Measures
DNA
Enzymes
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Urology

Cite this

Response of rat and human prostatic cancers to the novel 5α-reductase inhibitor, SK and F 105657. / Lamb, J. C.; Isaacs, John Tod; Johnson, R. K.; Isaacs, J. T.

In: Prostate, Vol. 21, No. 1, 1992, p. 15-34.

Research output: Contribution to journalArticle

Lamb, J. C. ; Isaacs, John Tod ; Johnson, R. K. ; Isaacs, J. T. / Response of rat and human prostatic cancers to the novel 5α-reductase inhibitor, SK and F 105657. In: Prostate. 1992 ; Vol. 21, No. 1. pp. 15-34.
@article{63ce56a97b6c444f9764c2df08766e8b,
title = "Response of rat and human prostatic cancers to the novel 5α-reductase inhibitor, SK and F 105657",
abstract = "The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R-3327 H and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5α-reductase inhibitor, SK and F 105657, was tested in vivo. SK and F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor and the human PC-82 tumor have a low to undetectable level of tissue 5α-reductase activity and both responded to SK and F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., >70{\%}) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat R-3327 H prostatic cancer has a much higher level of tissue 5α-reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK and F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R- 3327 G tumor-bearing rats which experienced an antitumor response. These results suggest that SK and F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5α-reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5α-reductase activity could be treated with SK and F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5α-reductase activity.",
author = "Lamb, {J. C.} and Isaacs, {John Tod} and Johnson, {R. K.} and Isaacs, {J. T.}",
year = "1992",
language = "English (US)",
volume = "21",
pages = "15--34",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Response of rat and human prostatic cancers to the novel 5α-reductase inhibitor, SK and F 105657

AU - Lamb, J. C.

AU - Isaacs, John Tod

AU - Johnson, R. K.

AU - Isaacs, J. T.

PY - 1992

Y1 - 1992

N2 - The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R-3327 H and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5α-reductase inhibitor, SK and F 105657, was tested in vivo. SK and F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor and the human PC-82 tumor have a low to undetectable level of tissue 5α-reductase activity and both responded to SK and F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., >70%) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat R-3327 H prostatic cancer has a much higher level of tissue 5α-reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK and F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R- 3327 G tumor-bearing rats which experienced an antitumor response. These results suggest that SK and F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5α-reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5α-reductase activity could be treated with SK and F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5α-reductase activity.

AB - The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R-3327 H and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5α-reductase inhibitor, SK and F 105657, was tested in vivo. SK and F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor and the human PC-82 tumor have a low to undetectable level of tissue 5α-reductase activity and both responded to SK and F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., >70%) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat R-3327 H prostatic cancer has a much higher level of tissue 5α-reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK and F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R- 3327 G tumor-bearing rats which experienced an antitumor response. These results suggest that SK and F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5α-reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5α-reductase activity could be treated with SK and F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5α-reductase activity.

UR - http://www.scopus.com/inward/record.url?scp=0026744010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026744010&partnerID=8YFLogxK

M3 - Article

C2 - 1641369

AN - SCOPUS:0026744010

VL - 21

SP - 15

EP - 34

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 1

ER -