dynorphins and Prostatic-Neoplasms

The effect of opiate receptor agonists upon cell growth of the prostatic carcinoma cell line DU145 were studied. Dynorphin-A increased growth significantly with a peak response at 10(-13) M, of 21 +/- 4% (mean +/- SEM). The dose response curve had a typical inverted-U shape. Dynorphin fragments 1-13 and 1-7 also increased growth at 10(-13) M, while the 2-13 fragment failed to increase growth. Naloxone increased growth at high concentration (10(-7) M) suggesting a stimulatory effect, while at the same time blocking the effect of dynorphin-A. This data demonstrates that agents which stimulate opiate receptors, especially the kappa receptor agonist dynorphin, increase the growth of prostatic carcinoma, and that this effect is controlled by changes at the N-terminal end of the peptide. This effect is blocked by Naloxone.

Topics: beta-Endorphin; Cell Division; Dose-Response Relationship, Drug; Dynorphins; Enkephalin, Leucine; Male; Morphine; Naloxone; Narcotics; Prostatic Neoplasms; Receptors, Opioid; Tumor Cells, Cultured