Salinomycin decreases feline sarcoma and carcinoma cell viability when combined with doxorubicin

Abstract

BackgroundCancer is a significant health threat in cats. Chemoresistance is prevalent in solid tumors. The ionophore salinomycin has anti-cancer properties and may work synergistically with chemotherapeutics. The purpose of our study was to determine if salinomycin could decrease cancer cell viability when combined with doxorubicin in feline sarcoma and carcinoma cells.ResultsWe established two new feline injection-site sarcoma cell lines, B4 and C10, and confirmed their tumorigenic potential in athymic nude mice. B4 was more resistant to doxorubicin than C10. Dose-dependent effects were not observed until 92 μM in B4 cells (p = 0.0006) vs. 9.2 μM (p = 0.0004) in C10 cells. Dose-dependent effects of salinomycin were observed at 15 μM in B4 cells (p = 0.025) and at 10 μM in C10 cells (p = 0.020). Doxorubicin plus 5 μM salinomycin decreased viability of B4 cells compared to either agent alone, but only at supra-pharmacological doxorubicin concentrations. However, doxorubicin plus 5 μM salinomycin decreased viability of C10 cells compared to either agent alone at doxorubicin concentrations that can be achieved in vivo (1.84 and 4.6 μM, p < 0.004). In SCCF1 cells, dose-dependent effects of doxorubicin and salinomycin were observed at 9.2 (p = 0.036) and 2.5 (p = 0.0049) μM, respectively. When doxorubicin was combined with either 1, 2.5, or 5 μM of salinomycin in SCCF1 cells, dose-dependent effects of doxorubicin were observed at 9.2 (p = 0.0021), 4.6 (p = 0.0042), and 1.84 (p = 0.0021) μM, respectively. Combination index calculations for doxorubicin plus 2.5 and 5 μM salinomycin in SCCF1 cells were 0.4 and 0.6, respectively.ConclusionsWe have developed two new feline sarcoma cell lines that can be used to study chemoresistance. We observed that salinomycin may potentiate (C10 cells) or work synergistically (SCCF1 cells) with doxorubicin in certain feline cancer cells. Further research is indicated to understand the mechanism of action of salinomycin in feline cancer cells as well as potential tolerability and toxicity in normal feline tissues.Electronic supplementary materialThe online version of this article (10.1186/s12917-019-1780-5) contains supplementary material, which is available to authorized users.

How does aggregation of doxorubicin molecules affect its solvation and membrane penetration?

“…DOX, also known as Adriamycin, is an antiproliferative drug that intercalates into the DNA, thus hampering the division of cancer cells and eventually inducing apoptosis. 3,4,[9][10][11][12][13][14] DOX as hydrochloride is water-soluble (B10 mg mL À1 ) and is injected in patients. Recently, the use of DOX formulations, especially polyethylene glycol encapsulated (PEGlated) or liposomal encapsulated DOX instead of pure DOX has helped to reduce the side effects such as cardiotoxicity.…”

“…Recently, the use of DOX formulations, especially polyethylene glycol encapsulated (PEGlated) or liposomal encapsulated DOX instead of pure DOX has helped to reduce the side effects such as cardiotoxicity. 3,4,11,13–16…”

“…Recently, the use of DOX formulations, especially polyethylene glycol encapsulated (PEGlated) or liposomal encapsulated DOX instead of pure DOX has helped to reduce the side effects such as cardiotoxicity. 3,4,11,[13][14][15][16] DOX is composed of a hydrophobic anthracycline unit (Scheme 1), substituted with two keto, two hydroxy, and a methoxy function at the aromatic core (rings A to C). A rather hydrophilic part of DOX is constituted from the amine and hydroxy functionalised oxane moiety with a hydroxymethyl and a b-hydroxycarbonyl group at the saturated end of the anthracycline core (ring D).…”

MicroRNA‑133b alleviates doxorubicin‑induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2

“…doxorubicin, a broad-spectrum antitumor drug, has been reported to effectively treat various types of cancer, including hepatocellular carcinoma, lung cancer and gastric cancer (1)(2)(3). However, the accumulation of doxorubicin in the body may lead to cardiotoxicity, which results in cardiomyocyte apoptosis and collagen deposition, ultimately leading to dilated cardiomyopathy and heart failure (4)(5)(6)(7).…”

Detection of Epithelial Cell Adhesion Molecule in Feline Normal and Tumor Cell Lines and Tissues With Selected Commercial Anti-human EpCAM Antibodies

“…Feline mammary epithelial cells (FMEC, p36–69, from Dr. John Parker, Cornell University) ( 28 ) and Norden Laboratory feline kidney (NLFK) cells (p41–93, from Dr. Colin Parrish, Cornell University) ( 29 ) were used as non-tumorigenic epithelial control cell lines. C10 injection site sarcoma cells (p43–66, from Dr. Kelly Hume, Cornell University) ( 30 ) were used as a non-epithelial tumor cell control. FMEC cells were grown in a 50/50 v/v mixture of DMEM and F12K (Ham's F-12K Nutrient Mixture, Kaighn's Modification with L-glutamine) with 10% FBS, 1% penicillin, and streptomycin, 1% non-essential amino acids (NEAA), and 10 ng/mL endothelial mitogen factor (MP Biomedicals, Fisher Scientific, Rockford, IL).…”