Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

Abstract

The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.

Transcriptomic insight into salinomycin mechanisms in breast cancer cell lines: synergistic effects with dasatinib and induction of estrogen receptor β

“…This pathway controls G1/S phase transition. Sal induces cell cycle arrest [53]. Fourteen out of 26 (54%) of the genes associated with the pathway were modulated by the drug, with 12 of them being downregulated.…”

Salinomycin: A new paradigm in cancer therapy

“…Salinomycin induced cell-cycle arrest and decreased expression of anti-apoptotic genes in MCF-7 cells, thereby causing apoptotic cell death of tumor cells, whereas non-tumor cells were able to evade this toxic effect. 86…”

“…Salinomycin induced cell-cycle arrest and decreased expression of anti-apoptotic genes in MCF-7 cells, thereby causing apoptotic cell death of tumor cells, whereas non-tumor cells were able to evade this toxic effect. 86 Salinomycin induced apoptosis in human T-cells of leukemia, but Fuchs et al 2 reported that normal human T-lymphocytes were not harmed. Salinomycin is more potent in inhibiting P-gp than verapamil, which is a known drug for inhibiting ABC transporter.…”

Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review

“…Despite the predominant antitumor effects and fewer adverse effects of Sal, the mechanism by which Sal brings about cancer cell death while non-malignant cells are exempted from the lethal effects remaining poorly understood. According to the studies both in vivo and in vitro, such following mechanisms that mitochondria-dependent cell death [ 20 , 21 ], Death receptor - mediated cell death [ 14 ], increased DNA damage and cell cycle arrest [ 22 , 23 ], p-glycoprotein inhibition [ 24 , 25 ] have been reported to involve the predominant anticancer effects of Sal. However, those mechanisms may just play a partial role in the anti-cancer effects of Sal as conventional chemotherapeutical agents rely on them to induce cancer cell death.…”