Salinomycin Radiosensitizes Human Nasopharyngeal Carcinoma Cell Line CNE-2 to Radiation

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2015 Jul 26

PMID 26209294

Citations 5

Authors

Yongqin Zhang

Yun Zuo

Zhifeng Guan

Weidong Lu

Zheng Xu

Hao Zhang

Yan Yang

Meilin Yang

Hongcheng Zhu

Xiaochen Chen

Affiliations

Soon will be listed here.

Abstract

Nasopharyngeal carcinoma (NPC) is primarily treated by chemoradiation. However, how to promote radiation sensitivity in NPC remains a challenge. Salinomycin is potentially useful for the treatment of cancer. This study aimed to explore the radiosensitivity of salinomycin on human nasopharyngeal carcinoma cell line CNE-2. CNE-2 were treated with salinomycin or irradiation, alone or in combination. The cytotoxicity effects of salinomycin were measured using CCK-8 assay. Clonogenic survival assay was used to evaluate the effects of salinomycin on the radiosensitivity of CNE-2. The changes of cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of Caspase3/Bax/Bal-2 was detected by Western blotting. DNA damage was detected via γ-H2AX foci counting. The results showed that salinomycin induced apoptosis and G2/M arrest, increased Bax and cleaved Caspase3, decreased Bcl-2 expression, and increased the formation of γ-H2AX nuclear foci. These data suggest that salinomycin may be a radiosensitizer for NPC radiotherapy.

Citing Articles

Radiosensitivity-Related Genes and Clinical Characteristics of Nasopharyngeal Carcinoma.

Dai Y, Zhang Y, Yang M, Zhou L, Pan H, Xiao T Biomed Res Int. 2020; 2020:1705867.

PMID: 33299859 PMC: 7704138. DOI: 10.1155/2020/1705867.

Enhanced anticancer effect of oncostatin M combined with salinomycin in CD133 HepG2 liver cancer cells.

Fu C, Wang L, Tian G, Zhang C, Zhao Y, Xu H Oncol Lett. 2019; 17(2):1798-1806.

PMID: 30675240 PMC: 6341778. DOI: 10.3892/ol.2018.9796.

PPARβ/δ Agonist GW501516 Inhibits Tumorigenicity of Undifferentiated Nasopharyngeal Carcinoma in C666-1 Cells by Promoting Apoptosis.

Ji Y, Li H, Wang F, Gu L Front Pharmacol. 2018; 9:648.

PMID: 30002625 PMC: 6031703. DOI: 10.3389/fphar.2018.00648.

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

Jiang J, Li H, Qaed E, Zhang J, Song Y, Wu R J Exp Clin Cancer Res. 2018; 37(1):26.

PMID: 29433536 PMC: 5809980. DOI: 10.1186/s13046-018-0680-z.

Effects of salinomycin and 17‑AAG on proliferation of human gastric cancer cells in vitro.

Zhang Z, Zhao J, Mi Z, Pang Q, Wang A, Chen M Mol Med Rep. 2017; 16(2):1063-1070.

PMID: 28627587 PMC: 5562019. DOI: 10.3892/mmr.2017.6735.

References

Fuchs D, Daniel V, Sadeghi M, Opelz G, Naujokat C . Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem Biophys Res Commun. 2010; 394(4):1098-104. DOI: 10.1016/j.bbrc.2010.03.138. View

Riccioni R, Dupuis M, Bernabei M, Petrucci E, Pasquini L, Mariani G . The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis. 2010; 45(1):86-92. DOI: 10.1016/j.bcmd.2010.03.008. View

Danforth H, Ruff M, REID W, Johnson J . Anticoccidial activity of salinomycin in floor-pen experiments with broilers. Poult Sci. 1977; 56(3):933-8. DOI: 10.3382/ps.0560933. View

Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C . Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun. 2009; 390(3):743-9. DOI: 10.1016/j.bbrc.2009.10.042. View

Akervall J, Nandalur S, Zhang J, Qian C, Goldstein N, Gyllerup P . A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck. Eur J Cancer. 2013; 50(3):570-81. DOI: 10.1016/j.ejca.2013.11.007. View

Le P, McDermott J, Jimeno A . Targeting the Wnt pathway in human cancers: therapeutic targeting with a focus on OMP-54F28. Pharmacol Ther. 2014; 146:1-11. PMC: 4304994. DOI: 10.1016/j.pharmthera.2014.08.005. View

Kim J, Chae M, Kim W, Kim Y, Kang H, Kim H . Salinomycin sensitizes cancer cells to the effects of doxorubicin and etoposide treatment by increasing DNA damage and reducing p21 protein. Br J Pharmacol. 2010; 162(3):773-84. PMC: 3041264. DOI: 10.1111/j.1476-5381.2010.01089.x. View

Zhi Q, Chen X, Ji J, Zhang J, Li J, Cai Q . Salinomycin can effectively kill ALDH(high) stem-like cells on gastric cancer. Biomed Pharmacother. 2011; 65(7):509-15. DOI: 10.1016/j.biopha.2011.06.006. View

Dong T, Zhou H, Wang L, Feng B, Lv B, Zheng M . Salinomycin selectively targets 'CD133+' cell subpopulations and decreases malignant traits in colorectal cancer lines. Ann Surg Oncol. 2011; 18(6):1797-804. DOI: 10.1245/s10434-011-1561-2. View

10.

Gupta P, Onder T, Jiang G, Tao K, Kuperwasser C, Weinberg R . Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009; 138(4):645-659. PMC: 4892125. DOI: 10.1016/j.cell.2009.06.034. View

11.

Zhang C, Yang X, Zhang Q, Yang B, Xu L, Qin Q . Berberine radiosensitizes human nasopharyngeal carcinoma by suppressing hypoxia-inducible factor-1α expression. Acta Otolaryngol. 2013; 134(2):185-92. DOI: 10.3109/00016489.2013.850176. View

12.

Zhang B, Wang X, Cai F, Chen W, Loesch U, Bitzer J . Effects of salinomycin on human ovarian cancer cell line OV2008 are associated with modulating p38 MAPK. Tumour Biol. 2012; 33(6):1855-62. DOI: 10.1007/s13277-012-0445-9. View

13.

Miyazaki Y, Shibuya M, Sugawara H, Kawaguchi O, Hirsoe C . Salinomycin, a new polyether antibiotic. J Antibiot (Tokyo). 1974; 27(11):814-21. DOI: 10.7164/antibiotics.27.814. View

14.

He L, Wang F, Dai W, Wu D, Lin C, Wu S . Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines. Pancreatology. 2013; 13(1):72-8. DOI: 10.1016/j.pan.2012.11.314. View

15.

Scherzed A, Hackenberg S, Froelich K, Rak K, Technau A, Radeloff A . Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro. Toxicol Lett. 2013; 218(3):207-14. DOI: 10.1016/j.toxlet.2013.02.001. View

16.

Wang Y . Effects of salinomycin on cancer stem cell in human lung adenocarcinoma A549 cells. Med Chem. 2011; 7(2):106-11. DOI: 10.2174/157340611794859307. View

17.

Verdoodt B, Vogt M, Schmitz I, Liffers S, Tannapfel A, Mirmohammadsadegh A . Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012; 7(9):e44132. PMC: 3446972. DOI: 10.1371/journal.pone.0044132. View

18.

Wang F, He L, Dai W, Xu Y, Wu D, Lin C . Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2013; 7(12):e50638. PMC: 3527475. DOI: 10.1371/journal.pone.0050638. View

19.

Kim K, Yu S, Lee S, Chun S, Choi Y, Park Y . Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization. Biochem Biophys Res Commun. 2011; 413(1):80-6. DOI: 10.1016/j.bbrc.2011.08.054. View

20.

Zhang G, Liang Y, Zhou L, Chen S, Chen G, Zhang T . Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells. Cancer Lett. 2011; 313(2):137-44. DOI: 10.1016/j.canlet.2011.05.030. View