Faculty Collaboration Database

Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil. Anticancer Res 2007;27(1A):107-16

Date

03/14/2007

Pubmed ID

17352222

Scopus ID

2-s2.0-33847650043 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

BACKGROUND: Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. P-glycoprotein (P-gp), the product of the multidrug resistance 1 (MDR1) gene, acts as an efflux pump and prevents sufficient intracellular accumulation of several anticancer agents, thus, playing a major role in MDR. Tamoxifen (Tam), ICI 182 780 (ICI) and Adriamycin (Adr) alone or with (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] possible effects on cell growth inhibition and regulation of MDR1, mRNA and P-gp expression were examined in both an MDR human breast cancer cell line, MCF-7/Adr cells, and primary cultured human breast cancer epithelial cells (PCHBCEC).

MATERIALS AND METHODS: Cells were treated with 0.05% of (-)-GPCSO either in the absence or presence of either 0.1 microM Tam, ICI or Adr for 24 h.

RESULTS: Using the non-radioactive cell proliferation MTS assay, none of these chemotherapeutic agents alone inhibited MCF-7/Adr cell and PCHBCEC proliferation; meanwhile, the combination of 0.1 microM Tam, ICI or Adr with 0.05% (-)-GPCSO significantly reduced MCF-7/Adr cell growth by approximately 34%, 32% and 23%, respectively, of that of the vehicle-treated cells. For PCHBCEC, the combination of 0.05% (-)-GPCSO with 0.1 microM of Tam, ICI and Adr reduced cell growth to about 94%, 90%, and 71% respectively, of the vehicle treated PCHBCEC. Furthermore, (-)-GPCSO inhibited MDR1/P-gp expression in both MCF- 7/Adr and PCHBCEC in a dose-dependent manner. Our results provide insight into the MDR-reversing potential of (-)-GPCSO in human breast cancer cells resistant to current chemotherapeutic agents.

Author List

Ye W, Chang HL, Wang LS, Huang YW, Shu S, Dowd MK, Wan PJ, Sugimoto Y, Lin YC

MESH terms used to index this publication - Major topics in bold

Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Cell Line, Tumor
Cottonseed Oil
Doxorubicin
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Drug Synergism
Estradiol
Gene Expression
Genes, MDR
Gossypol
Humans
RNA, Messenger
Tamoxifen
Tumor Cells, Cultured