Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity

Author(s): Jihene Elloumi-Mseddi, Dhouha Msalbi, Raouia Fakhfakh, Sami Aifa*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 19 , Issue 8 , 2019

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Abstract:

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.

Objective: In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).

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.

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.

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.

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

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Article Details

VOLUME: 19
ISSUE: 8
Year: 2019
Page: [1037 - 1047]
Pages: 11
DOI: 10.2174/1871520619666190118120030
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