title: 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 G1. Cells treated with aphidicolin to block cells at G1/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.
authors.affiliation: Radiopharmaceutical Research, Department of Radiology, The George Washington University Medical Center, Washington, DC 20037, USA.
authors.forename: P O
authors.initials: PO
authors.lastname: Zamora
authors.forename: T W
authors.initials: TW
authors.lastname: Moody
authors.forename: C S
authors.initials: CS
authors.lastname: John
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D010880:Piperidines / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D010880:Piperidines; D017480:Receptors, sigma; C084662:4-iodo-N-piperidinoethylbenzamide