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Differences in uptake and metabolism of retinoic acid between estrogen receptor-positive and -negative human breast cancer cells

Okamoto, K; Andreola, F; Chiantore, MV; Dedrick, RL; De Luca, LM; (2000) Differences in uptake and metabolism of retinoic acid between estrogen receptor-positive and -negative human breast cancer cells. CANCER CHEMOTH PHARM , 46 (2) 128 - 134.

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Abstract

Purpose: Our previous work had shown that retinoic acid (RA) inhibits cell growth and induces apoptosis in estrogen receptor-positive (ER-positive) MCF-7 and T-47D human breast carcinoma cells, but not in ER-negative human breast carcinoma cells MB-231 and MB-453, The purpose of this work was to determine whether these differences might be due to differences in uptake and metabolism of the drug between ER-positive and ER-negative cells. Methods: We measured RA uptake in cultured human breast cancer cells and determined its metabolism by high-pressure liquid chromatographic analysis, Results: The two ER positive cell lines reached maximum RA uptake at about 2 h, followed by a sharp decline, so that most RA had disappeared from the cells and from the medium by 24 h and was found as oxidation products in the culture medium. In contrast, the two ER-negative cell lines showed a pattern of lower accumulation without the sharp increase and subsequent steep decline, so that by 24 h there was more RA in these cells and their culture medium than in the RA-responsive ER-positive cells, even though at 2 h the ER-negative cells had taken up less RA than the ER-positive cells, Kinetic analysis of the uptake of RA in MCF-7 cells was consistent with rapid movement across the cell membranes and the actual rate determined by diffusion of albumin-bound retinoid to the cells. Conclusions: This study is the first to demonstrate profound differences in RA accumulation and confirms previous results on different rates of RA metabolism between ER-positive and ER-negative human breast cancer cells, The findings reported here, therefore, may introduce additional elements to be considered in the design of new drugs for cancer chemoprevention and therapy.

Type:Article
Title:Differences in uptake and metabolism of retinoic acid between estrogen receptor-positive and -negative human breast cancer cells
Keywords:free diffusion, retinoic acid uptake, breast cancer cells, GROWTH-INHIBITION, TISSUE TRANSGLUTAMINASE, IONIZATION BEHAVIOR, SERUM-ALBUMIN, DISPOSITION, RESISTANT, MICE

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