The effects of jatrophane derivatives on the reversion of MDR1- and MRP-mediated multidrug resistance in the MDA-MB-231 (HTB-26) cell line

Maria José U Ferreira, N. Gyémánt, Ana Margarida Madureira, M. Tanaka, Kitti Koós, Remigijus Didziapetris, J. Molnár

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Multidrug resistance (MDR) of cancer cells can be the result of a variety of mechanisms that are not completely understood. One of the most significant among them concerns altered membrane transport in tumor cells, often referred to as typical or classic MDR. This mechanism is related to the over-expression of a variety of proteins, that belong to the super family of ABC transporters. The aim or this study was to look for new effective modulators of MDR1 and multidrug resistance-associated protein (MRP) transporters. Ten diterpenes based on the jatrophane skeleton, including rearranged polycyclic derivatives, were studied on the MDA-MB-231 (HTB-26) human breast cancer cell line. The majority of those compounds were able to strongly enhance the rhodamine 123 accumulation of the human MDR1 gene transfected mouse lymphoma cell line, as previously described. In the present study, the MDR reversal of the same jatrophanes on MDR1- and MRP- mediated resistance of human breast cancer cells is reported. These cells simultaneously express MDR1 and MRP proteins when identified by monoclonal antibodies. However, in a functional assay, where rhodamine 123 accumulation was measured and verapamil was the traditional positive control, only MRP was active, while MDR1 was inactive. Carboxyfluorescein served as a substrate for MRP-mediated drug efflux, and indomethacine was the positive control used as an inhibitor of MRP in the flow cytometric experiments. The effectivity of various jatrophanes was different on the carboxyfluorescein efflux inhibition of the human breast cancer cells. These results may have importance in the planning of a new type of combination chemotherapy.

Original languageEnglish
Pages (from-to)4173-4178
Number of pages6
JournalAnticancer Research
Volume25
Issue number6 B
Publication statusPublished - Nov 2005

Fingerprint

Multidrug Resistance-Associated Proteins
Multiple Drug Resistance
Cell Line
Rhodamine 123
Breast Neoplasms
ATP-Binding Cassette Transporters
Diterpenes
Verapamil
Combination Drug Therapy
Skeleton
4-trifluoromethylsalicylic acid
jatrophane
Lymphoma
Neoplasms
Proteins
Monoclonal Antibodies
Membranes
Pharmaceutical Preparations
Genes

Keywords

  • Euphorbia
  • HTB-26 cell line
  • Jatrophane diterpenes
  • Multidrug resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The effects of jatrophane derivatives on the reversion of MDR1- and MRP-mediated multidrug resistance in the MDA-MB-231 (HTB-26) cell line. / Ferreira, Maria José U; Gyémánt, N.; Madureira, Ana Margarida; Tanaka, M.; Koós, Kitti; Didziapetris, Remigijus; Molnár, J.

In: Anticancer Research, Vol. 25, No. 6 B, 11.2005, p. 4173-4178.

Research output: Contribution to journalArticle

Ferreira, Maria José U ; Gyémánt, N. ; Madureira, Ana Margarida ; Tanaka, M. ; Koós, Kitti ; Didziapetris, Remigijus ; Molnár, J. / The effects of jatrophane derivatives on the reversion of MDR1- and MRP-mediated multidrug resistance in the MDA-MB-231 (HTB-26) cell line. In: Anticancer Research. 2005 ; Vol. 25, No. 6 B. pp. 4173-4178.
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