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Home / Publicações / Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein.

Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein.

  • Autores: Amaral L, Molnar J, Spengler G, Viveiros M
  • Journal: Anticancer Research
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Thioridazine+induces+apoptosis+of+multidrug-resistant+mouse+lymphoma+cells+transfected+with+the+human+ABCB1+and+inhibits+the+expression+of+P-glycoprotein

AIM:
Chlorpromazine has activity against a large variety of cancer types. However, this phenothiazine produces a plethora of serious side-effects. We have studied thioridazine (TZ), a phenothiazine neuroleptic that is much milder, for activity against multidrug-resistant (MDR) cancer cells, as well as against the overexpressed ABCB1 transporter (P-glycoprotein) that is the cause for the MDR phenotype of these cancer cells.

MATERIALS AND METHODS:
MDR mouse T-lymphoma cells, transfected with the human gene ABCB1 that codes for the transporter ABCB1, were incubated with TZ for various periods of time and examined for evidence of apoptosis. Concentrations of TZ were evaluated for activity against the ABCB1 transporter with the aid of an automated ethidium bromide (EB) method.

RESULTS:
TZ induces apoptosis of MDR cancer cell line, as well as inhibits the activity of the overexpressed ABCB1 transporter of these cells.

CONCLUSION:
Because thioridazine has been in moderately safe use for over 40 years for the therapy of psychosis, it has the potential to serve as an adjuvant with anticancer agents, rendering the a priori MDR cancer cells susceptible to the anticancer agent.

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About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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