Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

Abstract

The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

HDAC inhibitors enhance the lethality of low dose salinomycin in parental and stem-like GBM cells

“…an ionophore and part of its mechanism of action is thought to involve the formation of lipid-soluble complexes with cations, thereby facilitating bi-directional ion flux through lipid barriers by passive diffusion. 9 Salinomycin can alter cytosolic calcium concentrations in rabbit hearts and was shown to inhibit mitochondrial function in isolated mitochondria. 7,10 Another study argued that salinomycin-induced increase of cytosolic Ca 2+ was partially mediated by influx through the plasma membrane and partially by release of Ca 2+ stored in mitochondria.…”

Salinomycin causes dedifferentiation via the extracellular signal-regulated kinase (ERK) pathway in rabbit articular chondrocytes

“…In our previous studies, stress agents, such as ROS, were shown to regulate apoptosis, proliferation, differentiation, and inflammation in rabbit articular chondrocytes (22). Furthermore, Szkudlarek-Mikyo et al, reported that SAL regulates differentiation in adipocytes (18). However, there is a lack of data regarding the potential effects of SAL on differentiation.…”

“…SAL is widely used in veterinary medicine and has recently been shown to regulate cellular responses in various cell types (18). The pharmacological action of SAL has generated increased attention in recent years.…”

Stimulation of Eryptosis by Narasin

“…Narasin, a cationic ionophore [1] with antimicrobial activity [2][3][4][5] is fed to ruminant animals to improve feed efficiency [6,7]. It may accumulate in tissues of edible animals [8,9].…”