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Effect of Bortezomib, Daptomycin and Their Combination on Antiproliferation in U266 Multiple Myeloma Cell Line

Year 2025, Volume: 46 Issue: 2, 201 - 205, 30.06.2025
https://doi.org/10.17776/csj.1540090

Abstract

Multiple myeloma is the second most common hematological malignancy in adults. Although current treatment approaches extend survival to 6 to 10 years in multiple myeloma treatment, most patients relapse. This situation has led to the need for new therapeutic agents in the treatment of multiple myeloma. Daptomycin, a drug molecule isolated from Streotomyces roseosporus and used especially in infections caused by Gram-positive bacteria, has been shown in recent studies to suppress tumor migration and angiogenesis. Bortezomib is a chemotherapy drug currently used in the treatment of multiple myeloma. In this study, we determined the antiproliferative effect of Bortezomib and Daptomycin applications on the U266 multiple myeloma cell line by % cell viability analysis with the XTT method. In addition, we determined the apoptosis levels of U266 multiple myeloma cell lines by flow cytometry. In conclusion, we determined that the combined application of Bortezomib and Daptomycin increased the anticancer effect of Bortezomib alone in U266 multiple myeloma cell lines. In light of the data obtained from this study, we can say that the effect of Daptomycin added to Bortezomib in the treatment of multiple myeloma may contribute significantly to the treatment of the disease.

Supporting Institution

TÜBİTAK

Project Number

1919B012224550

References

  • [1] Firth, J., Haematology: multiple myeloma, Clinical Medicine, 19(1) (2019) 58-60.
  • [2] Kumar V., Abbas A.K, Aster J.C., Robin’s Basic Pathology. 10th ed. Elsevier, (2020).
  • [3] Anonymous, Cubicin (daptomycin) product information, Cubist Pharmaceuticals Inc., Lexington, MA, (2003).
  • [4] Larkin M., Daptomycin approved for skin and skin-structure infections, The Lancet Infectious Diseases, 3(11) (2003) 677.
  • [5] Marty F.M., Yeh W.W., Wennersten C.B., Venkataraman L., Albano E., Alyea E.P., ... & Pillai S.K., Emergence of a clinical daptomycin-resistant Staphylococcus aureus isolate during treatment of methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis, Journal of clinical microbiology, 44(2) (2006) 595-597.
  • [6] Poutsiaka D.D., Skiffington S., Miller K.B., Hadley S., Snydman, D.R., Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients, Journal of Infection, 54(6) (2007) 567-571.
  • [7] Streit J.M., Jones R.N., Sader H.S., Daptomycin activity and spectrum: a worldwide sample of 6737 clinical Gram-positive organisms, Journal of Antimicrobial Chemotherapy, 53(4) (2004) 669–674.
  • [8] Field-Smith A., Morgan G.J., Davies F.E., Bortezomib (Velcade™) in the treatment of multiple myeloma, Therapeutics and clinical risk management, 2(3) (2006) 271-279.
  • [9] Cho S.M., Lee H.J., Karuso P., Kwon H.J., Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans, The Journal of Antibiotics, 74(10) (2021) 726-733.
  • [10] Durusu İ.Z., Hüsnügil H.H., Ataş H., Biber A., Gerekçi S., Güleç E.A., Özen C., Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line, Leukemia Research, 55 (2017) 33-40.
  • [11] Terzi H., Altun A., Şencan M., In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line, Indian Journal of Medical Research, 150(6) (2019) 630-634.
  • [12] Bostancı H.E., Yıldız M.T., Kapancık S., Şahin Inan Z.D., Kılıç H.A., Özensoy Güler Ö., ... & Kaplancıklı Z.A., New benzimidazole derivatives containing hydrazone group as anticancer agents: Inhibition of carbonic anhydrase IX and molecular docking studies, Archiv der Pharmazie, 358(3) (2025) e2400930.
  • [13] Roccaro A.M., Vacca A., Ribatti D., Bortezomib in the treatment of cancer, Recent patents on anti-cancer drug discovery, 1(3) (2006) 397-403.
  • [14] Coux O., Tanaka K., Goldberg A.L., Structure and functions of the 20S and 26S proteasomes, Annual review of biochemistry, 65(1) (1996) 801-847.
  • [15] Hideshima T., The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma (MM) cells, Blood, 96 (2000) 461a.
  • [16] Ciechanover A., The ubiquitin–proteasome pathway: on protein death and cell life, The EMBO journal, 17(24) (1998) 7151-7160.
  • [17] Mujtaba T., Dou Q.P., Advances in the understanding of mechanisms and therapeutic use of bortezomib, Discovery medicine, 12(67) (2011) 471.
  • [18] Ruschak A.M., Slassi M., Kay L.E., Schimmer A.D., Novel proteasome inhibitors to overcome bortezomib resistance, Journal of the National Cancer Institute, 103(13) (2011) 1007-1017.
  • [19] Argyriou A.A., Iconomou G., Kalofonos H.P., Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literatüre, Blood, The Journal of the American Society of Hematology, 112(5) (2008) 1593-1599.
  • [20] Brignole C., Marimpietri D., Pastorino F., Nico B., Di Paolo D., Cioni M., ... & Ponzoni M., Effect of bortezomib on human neuroblastoma cell growth, apoptosis, and angiogenesis, Journal of the National Cancer Institute, 98(16) (2006) 1142-1157.
  • [21] Mortenson M.M., Schlieman M.G., Virudachalam S., Bold R.J., Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line, Cancer chemotherapy and pharmacology, 54 (2004) 343-353.
  • [22] Papandreou C.N., Logothetis C.J., Bortezomib as a potential treatment for prostate cancer, Cancer research, 64(15) (2004) 5036-5043.
  • [23] Giuliani N., Morandi F., Tagliaferri S., Lazzaretti M., Bonomini S., Crugnola M., ... & Rizzoli V., The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients, Blood, The Journal of the American Society of Hematology, 110(1) (2007) 334-338.
  • [24] Pillai S.K., Gold H.S., Sakoulas G., Wennersten C., Moellering Jr R.C., Eliopoulos G.M., Daptomycin nonsusceptibility in Staphylococcus aureus with reduced vancomycin susceptibility is independent of alterations in MprF, Antimicrobial agents and chemotherapy, 51(6) (2007) 2223-2225.
  • [25] Tally F.P., DeBruin M.F., Development of daptomycin for gram-positive infections, Journal of Antimicrobial Chemotherapy, 46(4) (2000) 523-526.
  • [26] Tran T.T., Munita J.M., Arias C.A., Mechanisms of drug resistance: daptomycin resistance, Annals of the New York Academy of Sciences, 1354(1) (2015) 32-53.
  • [27] Stefani S., Campanile F., Santagati M., Mezzatesta M.L., Cafiso V., Pacini G. Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: a review of the available evidence, International journal of antimicrobial agents, 46(3) (2015) 278-289.
Year 2025, Volume: 46 Issue: 2, 201 - 205, 30.06.2025
https://doi.org/10.17776/csj.1540090

Abstract

Project Number

1919B012224550

References

  • [1] Firth, J., Haematology: multiple myeloma, Clinical Medicine, 19(1) (2019) 58-60.
  • [2] Kumar V., Abbas A.K, Aster J.C., Robin’s Basic Pathology. 10th ed. Elsevier, (2020).
  • [3] Anonymous, Cubicin (daptomycin) product information, Cubist Pharmaceuticals Inc., Lexington, MA, (2003).
  • [4] Larkin M., Daptomycin approved for skin and skin-structure infections, The Lancet Infectious Diseases, 3(11) (2003) 677.
  • [5] Marty F.M., Yeh W.W., Wennersten C.B., Venkataraman L., Albano E., Alyea E.P., ... & Pillai S.K., Emergence of a clinical daptomycin-resistant Staphylococcus aureus isolate during treatment of methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis, Journal of clinical microbiology, 44(2) (2006) 595-597.
  • [6] Poutsiaka D.D., Skiffington S., Miller K.B., Hadley S., Snydman, D.R., Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients, Journal of Infection, 54(6) (2007) 567-571.
  • [7] Streit J.M., Jones R.N., Sader H.S., Daptomycin activity and spectrum: a worldwide sample of 6737 clinical Gram-positive organisms, Journal of Antimicrobial Chemotherapy, 53(4) (2004) 669–674.
  • [8] Field-Smith A., Morgan G.J., Davies F.E., Bortezomib (Velcade™) in the treatment of multiple myeloma, Therapeutics and clinical risk management, 2(3) (2006) 271-279.
  • [9] Cho S.M., Lee H.J., Karuso P., Kwon H.J., Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans, The Journal of Antibiotics, 74(10) (2021) 726-733.
  • [10] Durusu İ.Z., Hüsnügil H.H., Ataş H., Biber A., Gerekçi S., Güleç E.A., Özen C., Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line, Leukemia Research, 55 (2017) 33-40.
  • [11] Terzi H., Altun A., Şencan M., In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line, Indian Journal of Medical Research, 150(6) (2019) 630-634.
  • [12] Bostancı H.E., Yıldız M.T., Kapancık S., Şahin Inan Z.D., Kılıç H.A., Özensoy Güler Ö., ... & Kaplancıklı Z.A., New benzimidazole derivatives containing hydrazone group as anticancer agents: Inhibition of carbonic anhydrase IX and molecular docking studies, Archiv der Pharmazie, 358(3) (2025) e2400930.
  • [13] Roccaro A.M., Vacca A., Ribatti D., Bortezomib in the treatment of cancer, Recent patents on anti-cancer drug discovery, 1(3) (2006) 397-403.
  • [14] Coux O., Tanaka K., Goldberg A.L., Structure and functions of the 20S and 26S proteasomes, Annual review of biochemistry, 65(1) (1996) 801-847.
  • [15] Hideshima T., The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma (MM) cells, Blood, 96 (2000) 461a.
  • [16] Ciechanover A., The ubiquitin–proteasome pathway: on protein death and cell life, The EMBO journal, 17(24) (1998) 7151-7160.
  • [17] Mujtaba T., Dou Q.P., Advances in the understanding of mechanisms and therapeutic use of bortezomib, Discovery medicine, 12(67) (2011) 471.
  • [18] Ruschak A.M., Slassi M., Kay L.E., Schimmer A.D., Novel proteasome inhibitors to overcome bortezomib resistance, Journal of the National Cancer Institute, 103(13) (2011) 1007-1017.
  • [19] Argyriou A.A., Iconomou G., Kalofonos H.P., Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literatüre, Blood, The Journal of the American Society of Hematology, 112(5) (2008) 1593-1599.
  • [20] Brignole C., Marimpietri D., Pastorino F., Nico B., Di Paolo D., Cioni M., ... & Ponzoni M., Effect of bortezomib on human neuroblastoma cell growth, apoptosis, and angiogenesis, Journal of the National Cancer Institute, 98(16) (2006) 1142-1157.
  • [21] Mortenson M.M., Schlieman M.G., Virudachalam S., Bold R.J., Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line, Cancer chemotherapy and pharmacology, 54 (2004) 343-353.
  • [22] Papandreou C.N., Logothetis C.J., Bortezomib as a potential treatment for prostate cancer, Cancer research, 64(15) (2004) 5036-5043.
  • [23] Giuliani N., Morandi F., Tagliaferri S., Lazzaretti M., Bonomini S., Crugnola M., ... & Rizzoli V., The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients, Blood, The Journal of the American Society of Hematology, 110(1) (2007) 334-338.
  • [24] Pillai S.K., Gold H.S., Sakoulas G., Wennersten C., Moellering Jr R.C., Eliopoulos G.M., Daptomycin nonsusceptibility in Staphylococcus aureus with reduced vancomycin susceptibility is independent of alterations in MprF, Antimicrobial agents and chemotherapy, 51(6) (2007) 2223-2225.
  • [25] Tally F.P., DeBruin M.F., Development of daptomycin for gram-positive infections, Journal of Antimicrobial Chemotherapy, 46(4) (2000) 523-526.
  • [26] Tran T.T., Munita J.M., Arias C.A., Mechanisms of drug resistance: daptomycin resistance, Annals of the New York Academy of Sciences, 1354(1) (2015) 32-53.
  • [27] Stefani S., Campanile F., Santagati M., Mezzatesta M.L., Cafiso V., Pacini G. Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: a review of the available evidence, International journal of antimicrobial agents, 46(3) (2015) 278-289.
There are 27 citations in total.

Details

Primary Language English
Subjects Cancer Biology, Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Natural Sciences
Authors

Kübra Yılmaz 0009-0004-2266-5545

Ahmet Ozan Kaleci 0000-0003-4514-6209

Project Number 1919B012224550
Publication Date June 30, 2025
Submission Date August 28, 2024
Acceptance Date March 28, 2025
Published in Issue Year 2025Volume: 46 Issue: 2

Cite

APA Yılmaz, K., & Kaleci, A. O. (2025). Effect of Bortezomib, Daptomycin and Their Combination on Antiproliferation in U266 Multiple Myeloma Cell Line. Cumhuriyet Science Journal, 46(2), 201-205. https://doi.org/10.17776/csj.1540090