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

Kosuke Okamoto, Fausto Andreola, Maria V. Chiantore, Robert L. Dedrick, Luigi M. De Luca

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume46
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Breast cancer cells
  • Free diffusion
  • Retinoic acid uptake

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Differences in uptake and metabolism of retinoic acid between estrogen receptor-positive and -negative human breast cancer cells'. Together they form a unique fingerprint.

Cite this