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Global Health and Tropical Medicine

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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.
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The added effect of thioridazine in the treatment of drug-resistant tuberculosis.

The review by Grosset et al. in a recent issue of the
Journal is highly interesting, and rightly pictures a
bright horizon for the improved treatment of tuberculosis. However, there are alternative compounds
that can already provide considerable relief in compassionate
application of treatment for multidrugr
esistant and extensively drug-resistant tuberculosis
(MDR/XDR-TB) in the short term, and may offer an
important additional effect in treatment regimens due
to a special working mechanism, such as effl ux pump
inhibition.
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Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis.

BACKGROUND:
Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin.
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Mechanisms of Antibiotic Resistance in Salmonella: Efflux Pumps, Genetics, Quorum Sensing and Biofilm Formation.

Multidrug resistance (MDR) to antibiotics presents a serious therapeutic problem in the treatment of bacterial infections. The importance of this mechanism of resistance in clinical settings is reflected in the increasing number of reports of multidrug resistant isolates. In Salmonella enterica, the most common etiological agent of food borne salmonellosis worldwide, MDR is becoming a major concern.
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About GHTM

GHTM is a R&D Unit that brings together researchers 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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