The Effect of Quercetin on Cell Viability and Apoptotic Cell Death of Human Osteosarcoma Cell Line (U2-OS) in Vitro
Osteosarcoma is the most common bone cancer found in childhood and adolescents. However, major problems associated with chemotherapy still remain, particularly the frequent development of drug resistance. Hence, new therapeutic approaches that can further improve the efficiency by using quercetin are interesting. The purpose of this study was to investigate the effect of quercetin on cell viability and apoptotic cell death of human osteosarcoma cell line (U2-OS). The results showed that quercetin at 5 10 25 50 and 100 μM significantly decreased the percentage of viability of U2-OS cells in a dose-dependent manner. Quercetin could induce apoptosis in U2-OS cells resulting in a large DNA fragmentation. Our results suggested that quercetin can inhibit cell proliferation and induce apoptosis of U2-OS cells, and provided for further investigation of underlying mechanisms of quercetin on U2-OS cells applied for osteosarcoma therapy.
1. Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 2009; 125: 229-234.
2. Ottaviani G., Jaffe N. The epidemiology of osteosarcoma. In: Pediatric and Adolescent Osteosarcoma. Edited by Norman Jaffe, Oyvind S. Bruland, Stefan Bielack. New York: Springer; 2009. pp. 3-13.
3. Oertel S, Blattmann C, Rieken S, et al. Radiotherapy in the treatment of primary osteosarcoma--a single center experience. Tumori 2010; 96: 582- 588.
4. Won KY, Lee CH, Kim YW, Park YK. Primary giant-cell-rich osteosarcoma of the urinary bladder: usefulness of osteocalcin and osteonectin immunohistochemical staining and literature review. Pathology 2011; 43: 161-164.
5. Bielack SS, Carrle D, Hardes J, Schuck A, Paulussen M. Bone tumors in adolescents and young adults. Curr Treat Options Oncol 2008; 9: 67-80.
6. Mei Y, Wei D, Liu J. Reversal of multidrug resistance in KB cells with tea polyphenol antioxidant capacity. Cancer Biol Ther 2005; 4: 468-473.
7. Muldoon MF, Kritchevsky SB. Flavonoids and heart disease. BMJ 1996; 312: 458-459.
8. Taguri T, Tanaka T, Kouno I. Antimicrobial activity of 10 different plant polyphenols against bacteria causing food-borne disease. Biol Pharm Bull 2004; 27: 1965-1969.
9. Kang TB, Liang NC. Studies on the inhibitory effects of quercetin on the growth of HL-60 leukemia cells. Biochem Pharmacol 1997; 54: 1013-1018.
10. Yoshida M, Yamamoto M, Nikaido T. Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle. Cancer Res 1992; 52: 6676- 6681.
11. Yoshida M, Sakai T, Hosokawa N, et al. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett 1990; 260: 10-13.
12. Lee TJ, Kim OH, Kim YH, et al. Quercetin arrests G2/M phase and induces caspase-dependent cell death in U937 cells. Cancer Lett 2006; 240: 234- 242.
13. Granado-Serrano AB, Martin MA, Bravo L, Goya L, Ramos S. Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 2006; 136: 2715-2721.
14. Kuo PC, Liu HF, Chao JI. Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J Biol Chem 2004; 279: 55875-55885.
15. Akbas SH, Timur M, Ozben T. The effect of quercetin on topotecan cytotoxicity in MCF-7 and MDA-MB 231 human breast cancer cells. J Surg Res 2005; 125: 49-55.
16. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63.
17. Berndt K, Campanile C, Muff R, Strehler E, Born W, Fuchs B. Evaluation of quercetin as a potential drug in osteosarcoma treatment. Anticancer Res 2013; 33: 1297-1306.
18. Liang W, Li X, Li C, et al. Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells. Mol Med Rep 2011; 4: 1017-1023.
19. Mohseny AB, Machado I, Cai Y, et al. Functional characterization of osteosarcoma cell lines provides representative models to study the human disease. Lab Invest 2011; 91: 1195-1205.
20. Nam TW, Yoo CI, Kim HT, Kwon CH, Park JY, Kim YK. The flavonoid quercetin induces apoptosis and inhibits migration through a MAPK-dependent mechanism in osteoblasts. J Bone Miner Metab 2008; 26: 551-560.
21. Bortner CD, Oldenburg NB, Cidlowski JA. The role of DNA fragmentation in apoptosis. Trends Cell Biol 1995; 5: 21-26.
22. Stadelmann C, Lassmann H. Detection of apoptosis in tissue sections. Cell Tissue Res 2000; 301: 19-31.
23. Haghiac M, Walle T. Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cells. Nutr Cancer 2005; 53: 220-231.
24. Psahoulia FH, Drosopoulos KG, Doubravska L, Andera L, Pintzas A. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol Cancer Ther 2007; 6: 2591- 2599.
25. Kim YH, Lee DH, Jeong JH, Guo ZS, Lee YJ. Quercetin augments TRAIL-induced apoptotic death: involvement of the ERK signal transduction pathway. Biochem Pharmacol 2008; 75: 1946-1958.
26. Zhang JY, Yi T, Liu J, Zhao ZZ, Chen HB. Quercetin induces apoptosis via the mitochondrial pathway in KB and KBv200 cells. J Agric Food Chem 2013; 61: 2188-2195.
27. Men K, Duan X, Wei XW, et al. Nanoparticle-delivered quercetin for cancer therapy. Anticancer Agents Med Chem 2014; 14: 826-832.