Increased binding to sigma sites of N-[1′(2-piperidinyl)ethyl)-4-[I-125]-iodobenzamide (I-125-PAB) with onset of tumor cell proliferation

Abstract

This study evaluated if the density of sigma sites was modulated following stimulation of mitosis and progression through the cell cycle. The sigma ligand N-[1′(2-piperidinyl)ethyl)-4-[I-125]-iodobenzamide (I-125-PAB) was a binding probe on the mammary tumor cell lines T47D and MCF-7, and the prostate tumor cell line DU-145. Cells at low density and in log phase growth bound more I-125-IPAB than those at high density at or the near plateau phase. Stimulation of mitosis with insulin or fresh 10% serum increased I-125-IPAB binding in all three cell lines. In cell-cycle synchronized cells, the highest amount of binding was found in cells treated with colcemid to block cells in the M-phase, while the lowest amount of binding was found in cells treated with low serum to block the cells in G 1. Cells treated with aphidicolin to block cells at G 1/S also bound less than cells block in the M-phase. Collectively, these results support a direct correlation between I-125-PAB binding and proliferative status, and suggest an up-regulation of sigma binding sites prior to mitosis.