Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity

Author(s):

Jihene Elloumi-Mseddi, Dhouha Msalbi, Raouia Fakhfakh and Sami Aifa*   Pages 1037 - 1047 ( 11 )

Abstract:

<P>Background: Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates. </P><P> Objective: In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin). </P><P> Methods: Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity. </P><P> Results: Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect. </P><P> Conclusion: Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.</P>

Keywords:

Nifuroxazide, rifaximin, breast cancer, cytotoxicity, diarrhea, drug repositioning.

Affiliation:

Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, Sidi Mansour Road Km 6, BP 1177, 3018 Sfax, Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, Sidi Mansour Road Km 6, BP 1177, 3018 Sfax, Immunology Department, Habib Bourguiba Hospital, 3029 Sfax, Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, Sidi Mansour Road Km 6, BP 1177, 3018 Sfax

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