Cell lines

HCC cell lines HepG2, SMMC-7721 and BEL-7402

Preparation method

The solubility of this compound in DMSO is <1.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

0 ~ 25 μM

Applications

In HCC cells, Salinomycin inhibited cell proliferation, down-regulated PCNA level as well as decreased the proportion of HCC CD133+ cell subpopulations. Salinomycin also induced cell cycle arrest and apoptosis. Compared to the control group, Salinomycin significantly down-regulated β-catenin expression, and increased intracellular Ca2+ concentrations.

Animal models

Nude mice bearing HepG2 cells

Dosage form

4 and 8 mg/kg; i.p.; q.d., for 6 weeks

Applications

In nude mice bearing HepG2 cells, Salinomycin reduced the size of liver tumors. The results of immunohistochemistry and TUNEL staining also showed that Salinomycin inhibited cell proliferation and induced apoptosis in vivo. Further study implied that the anti-tumor effects of Salinomycin were achieved by increasing intracellular Ca2+ levels, and subsequently inhibiting Wnt/β-catenin signaling.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

IC50: 7.7, 13.7 and 10.4 μM for HepG2, SMMC-7721 and BEL-7402 cell line, respectively (after 24h treatment)

Salinomycin (Sal), which is a polyether ionophore antibiotic from Streptomyces albus, has been proven to be able to kill different types of human cancer cells, most likely via interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, or other pathways.

In vitro: Several hepatocellular carcinoma (HCC) cell lines were treated with Sal. Results showed that Sal inhibited proliferation and decreased PCNA levels. Cell cycle analysis showed that Sal caused cell cycle arrest in different phases. Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio. Compared to control, β-catenin expression was down-regulated by Sal treatment significantly. The Ca2+ concentration in HCC cells was examined by flow cytometry and it was found that higher Ca2+ concentrations were observed in Sal treatment groups [1].

In vivo: The in vivo anti-tumor effect of Sal was verified using the hepatoma orthotopic tumor model and results showed that the liver tumor size in Sal-treated groups decreased. Immunohistochemistry and TUNEL staining also demonstrated that Sal could in vivo inhibit proliferation and induced apoptosis [1].

Clinical trial: N/A

Reference:
[1] Wang F,He L,Dai WQ,Xu YP,Wu D,Lin CL,Wu SM,Cheng P,Zhang Y,Shen M,Wang CF,Lu J,Zhou YQ,Xu XF,Xu L,Guo CY. Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. PLoS One.2012;7(12):e50638.