PMID: 1386843Jul 1, 1992Paper

Toremifene and its metabolites enhance doxorubicin accumulation in estrogen receptor negative multidrug resistant human breast cancer cells

Investigational New Drugs
V J WiebeM DeGregorio

Abstract

The enhanced accumulation of doxorubicin by agents known to reverse multidrug resistance provides a good functional test for evaluating modulating activity. In the present study, the non-steroidal triphenylethylene toremifene selectively increased doxorubicin accumulation in multidrug resistant estrogen receptor negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50 = less than 0.1 microgram/ml MDA 231; IC 50 = 100 micrograms/ml MDA A-1). Total accumulation of doxorubicin, expressed as area under the time concentration curve (AUC), was increased significantly in doxorubicin resistant cells (156% increase) versus wild type MDA 231 cells (6% increase). Correction of the accumulation defect to doxorubicin in drug resistant cells required a 18-20 hour pre-incubation with toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed by flow cytometric techniques. Toremifene had a dose response relationship in blocking cells in G0-G1 reducing the number of cells entering S phase of the cell cycle. This effect was maximal at concentrations which increased the accumulation of doxorubicin in MDA A-1 cells. Several metaboli...Continue Reading

References

Sep 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M W DeGregorioV J Wiebe
Apr 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M M Gottesman, I Pastan
Jun 21, 1989·Journal of the National Cancer Institute·B A Chabner, A Fojo
Aug 1, 1986·British Journal of Cancer·L M SlaterS Gupta
Jan 13, 1984·Biochemical and Biophysical Research Communications·H Y Lam
Dec 1, 1982·Cancer Chemotherapy and Pharmacology·M W DeGregorioJ R Wilbur

Citations

Jan 1, 1994·Breast Cancer Research and Treatment·S KoesterM W DeGregorio
Jan 1, 1993·Cancer Chemotherapy and Pharmacology·G T WurzV J Wiebe
Jan 1, 1993·Cytotechnology·J M Ford, W N Hait
Jul 28, 2005·Cancer Chemotherapy and Pharmacology·M W DeGregorioK W Turteltaub
Mar 25, 2000·Surgical Oncology·N K Ibrahim, G N Hortobagyi
Jul 1, 1998·The Breast Journal·N K Ibrahim, G N Hortobagyi
Feb 11, 2014·International Journal of Cancer. Journal International Du Cancer·Gregory T Wurz, M W DeGregorio
May 18, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eleftherios P MamounasNorman Wolmark
Dec 7, 2016·Menopause : the Journal of the North American Menopause Society·Chiao-Jung KaoM W DeGregorio

Related Concepts

Antineoplastic Agents
Mammary Neoplasms, Human
High Pressure Liquid Chromatography Procedure
Adriamycin
Drug Interactions
Drug Resistance
Flow Cytometry
Estrogen Nuclear Receptor
Zitazonium
Tumor Cells, Cultured

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Lipidomics & Rhinovirus Infection

Lipidomics can be used to examine the lipid species involved with pathogenic conditions, such as viral associated inflammation. Discovered the latest research on Lipidomics & Rhinovirus Infection.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Torsion Dystonia

Torsion dystonia is a movement disorder characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Here is the latest research.

Archaeal RNA Polymerase

Archaeal RNA polymerases are most similar to eukaryotic RNA polymerase II but require the support of only two archaeal general transcription factors, TBP (TATA-box binding protein) and TFB (archaeal homologue of the eukaryotic general transcription factor TFIIB) to initiate basal transcription. Here is the latest research on archaeal RNA polymerases.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.