Modulation of multidrug resistance and apoptosis of cancer cells by selected carotenoids.
The multidrug resistance (MDR) proteins that belong to the ATP-binding casette superfamily are present in a majority of human tumors and are an important final cause of therapeutic failure. Therefore, compounds which inhibit the function of the MDR-efflux proteins may improve the cytotoxic action of anticancer chemotherapy. The effects of carotenoids were studied on the activity of the MDR-1 gene-encoded efflux pump system. The carotenoids, isolated from paprika and other vegetables, were tested on the rhodamine 123 accumulation of human MDR-1 gene-transfected L1210 mouse lymphoma cells and human breast cancer cells MDA-MB-231 (HTB-26). Capsanthin and capsorubin enhanced the rhodamine 123 accumulation 30-fold relative to nontreated lymphoma cells. Lycopene, lutein, antheraxanthin and violaxanthin had moderate effects, while alfa- and beta-carotene had no effect on the reversal of MDR in the tumor cells. Apoptosis was induced in human MDR1 transfected mouse lymphoma cells and human breast cancer MDA-MB-231 (HTB-26) cell lines in the presence of lycopene, zeaxanthin and capsanthin. The data suggest the potential of carotenoids as possible resistance modifiers in cancer chemotherapy.
Molnár
Joseph
J
Institute of Medical Microbiology and Immunology, University of Szeged, Hungary. molnarj@comser.szote.u-szeged.hu
Gyémánt
Nóra
N
Mucsi
Ilona
I
Molnár
Annamária
A
Szabó
Margaret
M
Körtvélyesi
Tamás
T
Varga
András
A
Molnár
Péter
P
Tóth
Gyula
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002212:Capsicum / Q000737:chemistry; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019450:Genes, MDR; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D020112:Rhodamine 123 / Q000378:metabolism; D014162:Transfection
D010936:Plant Extracts; D020112:Rhodamine 123; D002338:Carotenoids