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Titolo:
REVERSAL OF MULTIDRUG-RESISTANCE IN-VIVO BY DIETARY ADMINISTRATION OFTHE PHYTOCHEMICAL INDOLE-3-CARBINOL
Autore:
CHRISTENSEN JG; LEBLANC GA;
Indirizzi:
N CAROLINA STATE UNIV,DEPT TOXICOL,BOX 7633 RALEIGH NC 27695 N CAROLINA STATE UNIV,DEPT TOXICOL RALEIGH NC 27695
Titolo Testata:
Cancer research
fascicolo: 3, volume: 56, anno: 1996,
pagine: 574 - 581
SICI:
0008-5472(1996)56:3<574:ROMIBD>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACID REACTION-PRODUCTS; HUMAN-LEUKEMIC-CELLS; P-GLYCOPROTEIN; VINCRISTINE RESISTANCE; P388 LEUKEMIA; CYTO-TOXICITY; INVITRO; CANCER; EXPRESSION; ADRIAMYCIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
J.G. Christensen e G.A. Leblanc, "REVERSAL OF MULTIDRUG-RESISTANCE IN-VIVO BY DIETARY ADMINISTRATION OFTHE PHYTOCHEMICAL INDOLE-3-CARBINOL", Cancer research, 56(3), 1996, pp. 574-581

Abstract

A major obstacle to successful cancer chemotherapy is the developmentof multidrug resistance (MDR) by cancer cells. MDR is characterized by enhanced cellular efflux of many structurally and functionally diverse compounds, including many anticancer drugs, due to overexpression of the MDR-1 gene product, P-glycoprotein, We hypothesized that the phytochemical, indole-3-carbinol (I3C), and some of its acid-condensationderivatives may inhibit P-glycoprotein-mediated transport due to their aromatic and nitrogen components, thus increasing the accumulation and efficacy of anticancer drugs and acting as a dietary adjuvant to conventional chemotherapy, I3C was subjected to acid conditions similar to those occurring in the stomach following ingestion and three acid-condensation products; a dimer, a noncyclic trimer, and a cyclic trimerwere isolated and purified by high-performance liquid chromatography,The ability of I3C and its acid-condensation derivatives to reverse MDR was investigated using murine B16 melanoma cells that were transfected with the human MDR-1 gene (B16/hMDR-1 cells) and were cross-resistant to vinblastine and doxorubicin. The I3C acid-condensation product mixture, but not I3C, sensitized B16/hMDR-1 transfectants to the toxicity of vinblastine and doxorubicin. All three I3C acid-condensation products also increased the accumulation of the P-glycoprotein substrate, doxorubicin, in B16/hMDR-1 transfectants to levels comparable to parental B16 cells. The I3C acid-condensation product mixture competed with azidopine for binding to P-glycoprotein, suggesting that the observed MDR-reversing effect of the acid-condensation products was due to direct interaction with P-glycoprotein, The ability of p.o. administered I3C to reverse MDR was also tested in vivo, The resistance of B16/hMDR-1 transfectants to vinblastine and doxorubicin was preserved after i.p. injection and growth in nude mice, Tumor mass in mice that were provided with 333 or 500 mg/kg mouse/day I3C in their diet and injecteds.c. with the anticancer drugs doxorubicin or vinblastine was significantly reduced as compared to tumor mass in mice provided with standard diet and injected with these anticancer drugs or mice provided with 500 mg/kg mouse/day I3C and not injected with anticancer compound, Theconcentrations of I3C used had no effect on survival or the general appearance and behavior of the mice, Collectively, these results indicate that ingestion of the common dietary constituent I3C results in itsconversion to acid-condensation derivatives that sensitized MDR tumors to chemotherapeutic drugs without eliciting direct toxicity to the host.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 03:15:52