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Antitumor activity of antiestrogenic phenylindoles on experimental prostate tumors
M R Schneider1, E von Angerer, W Höhn
1Institut für Pharmazie, Universität Regensburg, F.R.G.
Abstract:
Two antiestrogenic phenylindoles (D 16726 and D 15413) were tested for their prostatic tumor-inhibiting activity. Both compounds exerted a strong inhibitory effect on prostate and seminal vesicle weight of intact rats and mice comparable to that of diethylstilbestrol. Their estrogenic properties, however, are much lower than those of DES. Therefore, there is no direct correlation between estrogenic potency and inhibition of accessory sex organ weights. The tumor-inhibiting activity of D 16726 and D 15413 on the androgen-dependent R 3327 Dunning prostatic carcinoma and the human prostatic tumor PC 82 implanted in nude mice equals that of castration or of diethylstilbestrol. Both 2-phenylindoles had good affinities for estrogen receptors from calf uterine and R 3327 tumor cytosol, but no affinities for androgen and progesterone receptors. As these 2-phenylindoles have much lower estrogenic properties than diethylstilbestrol, they may also have low side-effects, and can therefore be of interest for the therapy of the prostatic carcinoma.
Insights
Two novel antiestrogenic phenylindoles show significant prostate tumor inhibition, comparable to diethylstilbestrol but with lower estrogenic effects. These compounds may offer a promising, lower-side-effect therapy for prostate cancer.
Area of Science:
- Pharmacology
- Oncology
- Endocrinology
Background:
- Prostate cancer is a significant health concern.
- Diethylstilbestrol (DES) is used to treat prostate cancer but has significant side effects.
- Novel therapeutic agents with improved side-effect profiles are needed.
Purpose of the Study:
- To evaluate the prostatic tumor-inhibiting activity of two antiestrogenic phenylindoles, D 16726 and D 15413.
- To compare their efficacy and estrogenic properties with diethylstilbestrol (DES).
- To assess their potential as therapeutic agents for prostate carcinoma.
Main Methods:
- Testing antiestrogenic phenylindoles (D 16726, D 15413) for prostatic tumor-inhibiting activity in rats and mice.
- Assessing effects on prostate and seminal vesicle weight.
- Evaluating tumor-inhibiting activity on androgen-dependent R 3327 Dunning prostatic carcinoma and human PC 82 tumors in nude mice.
- Determining receptor affinities for estrogen, androgen, and progesterone receptors.
Main Results:
- Both D 16726 and D 15413 significantly inhibited prostate and seminal vesicle weight, similar to DES.
- Estrogenic properties of these phenylindoles were considerably lower than DES.
- Tumor-inhibiting activity in animal models was comparable to castration or DES.
- Compounds showed affinity for estrogen receptors but not androgen or progesterone receptors.
Conclusions:
- There is no direct correlation between estrogenic potency and the inhibition of accessory sex organ weights.
- The antiestrogenic phenylindoles D 16726 and D 15413 demonstrate potent anti-tumor activity against prostate cancer models.
- Their lower estrogenic activity suggests a potential for reduced side effects, making them promising candidates for prostate carcinoma therapy.