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Cytotoxic effects of curcumin on osteosarcoma cell lines

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Summary

Curcumin (diferuloylmethane), one of the main components of the Indian spice turmeric, is known to possess potent anti-inflammatory and anti-oxidant properties. In addition, curcumin has also been shown to have in vitro and in vivo efficacy against a variety of malignancies. In the current study we examined the cytotoxic effect of curcumin on seven osteosarcoma (OS) cell lines with varying degrees of in vivo metastatic potential. Curcumin inhibited the growth of all OS cell lines tested with half-maximal inhibitory concentration values ranging from 14.4 to 24.6 μM. Growth inhibition was associated with a dose dependent increase in the number of apoptotic cells and accumulation of cells in the G2/M phase of the cell cycle. Curcumin treatment also resulted in cleavage of caspase-3 and poly adenosine diphosphate-ribose polymerase. Moreover, curcumin treatment was associated with an increase in cellular levels of the apoptotic B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein and a decrease in cellular content of the anti-apoptotic protein Bcl-2. In addition, curcumin treatment also inhibited the migration of OS cell lines. These data indicate that the potent cytotoxic activity of curcumin on OS cell lines is mediated by induction of apoptotic processes. Thus, curcumin has potential to be a novel OS chemotherapeutic agent.

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References

  1. Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9:422–441

    Article  PubMed  Google Scholar 

  2. Meyers PA, Heller G, Healey JH, Huvos A, Applewhite A, Sun M, LaQuaglia M (1993) Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol 11:449–453

    PubMed  CAS  Google Scholar 

  3. Weinfeld MS, Dudley HR (1962) Osteogenic sarcoma: a follow-up study of the ninety-four cases observed at the Massachusetts General Hospital from 1920 to 1960. Am J Orthop 44:269–276

    Google Scholar 

  4. Friedman MA, Carter S (1972) The therapy of osteogenic sarcoma: current status and thoughts for the future. J Surg Oncol 4:482–510

    Article  PubMed  CAS  Google Scholar 

  5. Link MP, Goorin AM, Horowitz M, Meyer WH, Belasco J, Baker A, Ayala A, Shuster J (1991) Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the multi-institutional osteosarcoma study. Clin Orthop Relat Res 270:8–14

    PubMed  Google Scholar 

  6. Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J (1987) Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol 5:21–26

    PubMed  CAS  Google Scholar 

  7. Baum ES, Gaynon P, Greenberg L, Krivit W, Hammond D (1981) Phase II trail cisplatin in refractory childhood cancer: children’s cancer study group report. Cancer Treat Rep 65:815–822

    PubMed  CAS  Google Scholar 

  8. Smith MA, Ungerleider RS, Horowitz ME, Simon R (1991) Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma. J Natl Cancer Inst 83:1460–1470

    Article  PubMed  CAS  Google Scholar 

  9. Meistrich ML, Chawla SP, da Cunha MF, Johnson SL, Plager C, Papadopoulos NE, Lipshultz LI, Benjamin RS (1989) Recovery of sperm production after chemotherapy for osteosarcoma. Cancer 63:2115–2123

    Article  PubMed  CAS  Google Scholar 

  10. Govindarajan VS (1980) Turmeric: chemistry, technology and quality. Crit Rev Food Sci Nutr 12:199–301

    Article  PubMed  CAS  Google Scholar 

  11. Amon HP, Wahl M (1991) Pharmacology of Curcuma longa. Plant Med 57:1–7

    Article  Google Scholar 

  12. Kunchandy E, Rao MNA (1990) Oxygen radical scavenging activity of curcumin. Int J Pharm 58:237–240

    Article  CAS  Google Scholar 

  13. Chan MM, Huang HI, Fenton MR, Fong D (1998) In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol 55:1955–1962

    Article  PubMed  CAS  Google Scholar 

  14. Sharma RA, Gescher AJ, Steward W (2005) Curcumin: the story so far. Eur J Cancer 41:1955–1968

    Article  PubMed  CAS  Google Scholar 

  15. Aggarwal BB, Kumar A, Bharti A (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:3633–3698

    Google Scholar 

  16. Dorai T, Gehani N, Katz A (2000) Therapeutic potential of curcumin in human prostate cancer. Prostate Cancer Dis 3:84–93

    Article  CAS  Google Scholar 

  17. Huang MT, Lou YR, Xie JG, Ma W, Lu YP, Yen P, Zhu BT, Newmark H, Ho CT (1998) Effect of dietary curcumin and dibenzoylmethane on formation of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and lymphomas/leukemias in Sencar mice. Carcinogenesis 19:1967–1700

    Google Scholar 

  18. Hanif R, Qiao L, Shiff SJ, Rigas B (1997) Curcumin, a natural plant phenolic food additive inhibits cell proliferation and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathway. J Lab Clin Med 130:576–584

    Article  PubMed  CAS  Google Scholar 

  19. Johnson JJ, Mukhtar H (2007) Curcumin for chemoprevention of colon cancer. Cancer Lett 255:170–181

    Article  PubMed  CAS  Google Scholar 

  20. Walters DK, Muff R, Langsam B, Gruber P, Born W, Fuchs B (2007) Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines. Invest New Drugs 25:305–312

    Article  PubMed  CAS  Google Scholar 

  21. Boersma HH, Kietselaer B, Stolk L, Bennaghmouch A, Hofstra L, Narula J, Heidendal G, Reutelingsperger C (2005) Past, present, and future of annexin A5: from protein discovery to clinical applications. J Nucl Med 46:2035–2050

    PubMed  CAS  Google Scholar 

  22. Konopleva M, Zhao S, Xie Z, Segall H, Younes A, Claxton DF, Estrov Z, Kornblau SM, Andreeff M (1999) Apoptosis. Molecules and mechanisms. Adv Exp Med Biol 457:217–236

    PubMed  CAS  Google Scholar 

  23. Shankar S, Srivastava RK (2007) Bax and Bak genes are essential for maximum apoptotic response by curcumin, a polyphenolic compound and cancer chemopreventive agent derived from turmeric, Curcuma longa. Carcinogenesis 28:1277–1286

    Article  PubMed  CAS  Google Scholar 

  24. Chen HW, Yu SL, Chen JJ, Li HN, Lin YC, Yao PL, Chou HY, Chien CT, Chen WJ, Lee YT, Yang PC (2004) Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol Pharmacol 65:99–110

    Article  PubMed  CAS  Google Scholar 

  25. Jaiswal AS, Marlow BP, Gupta N, Narayan S (2002) Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuloylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21:8414–8427

    Article  PubMed  CAS  Google Scholar 

  26. Hsu CH, Cheng AL (2007) Clinical studies with curcumin. Adv Exp Med Biol 595:471–480

    Article  PubMed  Google Scholar 

  27. Gupta KK, Bharne SS, Rathinasamy K, Naik NR, Panda D (2006) Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding. FEBS J 273:5320–5332

    Article  PubMed  CAS  Google Scholar 

  28. Kuo ML, Huang TS, Lin JK (1996) Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. Biochim Biophys Acta 1317:95–100

    PubMed  CAS  Google Scholar 

  29. Chen H, Zhang ZS, Zhang YL, Zhou DH (1999) Curcumin inhibits cell proliferation by interfering with the cell cycle and inducing apoptosis in colon carcinoma cells. Anticancer Res 19:3675–3680

    PubMed  CAS  Google Scholar 

  30. Mehta K, Pantazis P, McQueen T, Aggarwal DH (1997) Antiproliferative effects of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs 8:470–481

    Article  PubMed  CAS  Google Scholar 

  31. Er E, Oliver L, Cartron P-F, Juin P, Manon S, Vallette FM (2006) Mitochondria as the target of the pro-apoptotic protein Bax. Biochim Biophys Acta 1757:1301–1311

    Article  PubMed  CAS  Google Scholar 

  32. Murphy KM, Ranganathan V, Farnsworth ML, Kavallaris M, Lock RB (2000) Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ 7:102–111

    Article  PubMed  CAS  Google Scholar 

  33. Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci USA 95:14681–14686

    Article  PubMed  CAS  Google Scholar 

  34. Shankar S, Srivastava RK (2007) Involvement of Bcl-2 family members, phosphatidylinositol 3′-kinase/AKT and mitochondrial p53 in curcumin (diferuloylmethane)-induced apoptosis in prostate cancer. Int J Oncol 30:905–918

    PubMed  CAS  Google Scholar 

  35. Mukherjee NCS, Ghosh U, Bhattacharyya NP, Bhattacharya RK, Dey S, Roy M (2007) Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity. Mol Cell Biochem 297:31–39

    Article  CAS  Google Scholar 

  36. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB (2002) Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis 23:143–150

    Article  PubMed  CAS  Google Scholar 

  37. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D, Alessandro N (2005) Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett 224:53–65

    PubMed  CAS  Google Scholar 

  38. Bischt S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A, Maitra A (2007) Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. Journal of Nanobiotechnology 5:3

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by a grant from the Walter L. and Johanna Wolf Foundation, Zurich, Switzerland, the Schweizerischer Verein Balgrist and the University of Zurich. We also thank Dr. Nicole Bodmer for her contribution and input.

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Authors and Affiliations

  1. Laboratory for Orthopaedic Research, Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008, Zürich, Switzerland

    Denise K. Walters, Roman Muff, Bettina Langsam, Walter Born & Bruno Fuchs

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  1. Denise K. Walters
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  2. Roman Muff
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  3. Bettina Langsam
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  4. Walter Born
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  5. Bruno Fuchs
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Correspondence to Bruno Fuchs.

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Walters, D.K., Muff, R., Langsam, B. et al. Cytotoxic effects of curcumin on osteosarcoma cell lines. Invest New Drugs 26, 289–297 (2008). https://doi.org/10.1007/s10637-007-9099-7

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  • DOI: https://doi.org/10.1007/s10637-007-9099-7

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