Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, Sidi Mansour Road Km 6, BP 1177, 3018 Sfax, Tunisia.
Immunology Department, Habib Bourguiba Hospital, 3029 Sfax, Tunisia.
Anticancer Agents Med Chem. 2019;19(8):1037-1047. doi: 10.2174/1871520619666190118120030.
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.
In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).
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.
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.
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.
药物重定位正在成为选择新抗癌药物的理想策略。特别是，治疗化疗副作用的药物是最佳候选药物。
在本研究中，我们评估了两种止泻药（硝呋太尔和利福昔明）的抗肿瘤活性。
通过 MTT 分析、Brdu 掺入、线粒体通透性和 caspase-3 活性评估对乳腺癌细胞（MDA-MB-231、MCF-7 和 T47D）的增殖抑制作用。
两种药物均对 MCF-7、T47D 和 MDA-MB-231 细胞表现出细胞毒性作用。在 24、48 和 72 小时的治疗后，MCF-7 细胞的最低 IC50 值，而 T47D 和 MDA-MB-231 细胞则更具抗性。72 小时治疗后，T47D 和 MDA-MB-231 细胞的 IC50 值显著降低，显示出迟发性细胞毒性作用，尤其是硝呋太尔，但仍不如 MCF-7 细胞重要。根据 IC50 值，非肿瘤细胞系 HEK293 似乎对细胞毒性的敏感性较低，尤其是对利福昔明。两种药物均表现出 rhodamine 123 的积累，随着浓度的升高而增加，而 Brdu 掺入减少。尽管处理和未处理的 MCF-7 细胞之间的细胞周期没有显著差异，但 caspase-3 活性随着药物浓度的升高而增加，表明存在凋亡作用。
硝呋太尔和利福昔明用于克服抗癌药物的腹泻副作用。然而，它们已被证明是抗肿瘤药物，这使它们成为对抗癌症和化疗副作用的潜在双重有效药物。
