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Article

Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis

  • Authors:
    • Rui‑Fang Fan
    • Yu‑Xin Chen
    • Zhi‑Gang Fang
    • Xiao‑Yan Guo
    • Ying Lu
    • Ling‑Ling Liu
    • Yi‑Chuan Xu
    • Xiang‑Fu Liu
    • Dong‑Jun Lin
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong 510010, P.R. China, Department of Blood Transfusion, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
  • Pages: 5660-5666
    |
    Published online on: November 21, 2016
       https://doi.org/10.3892/mmr.2016.5957
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Abstract

Zoledronic acid (ZOL), a nitrogen‑containing bisphosphonate, is widely used in metastatic bone disease. Previous studies indicate that ZOL has marked anti‑leukemia activity, however, the underlying mechanism of action remains to be elucidated. The present study aimed to explore the mechanism of the anti‑leukemia effect of ZOL in leukemia cells. It was observed that ZOL inhibited the proliferation of HL‑60 and adriamycin‑resistant HL‑60 (HL‑60/A) cells using a WST‑8 assay. An Annexin V‑propidium iodide indicated that ZOL induced apoptosis of the two cell types in a dose‑ and time‑dependent manner. Hoechst 33342 staining was also used to verify the levels of apoptosis. The colony formation assay demonstrated that ZOL significantly inhibited colony formation capacity in acute myeloid leukemia (AML) cells. This was achieved by the induction of S‑phase cell cycle arrest, downregulation of B‑cell lymphoma 2 (Bcl‑2) and upregulation of Bcl‑2 associated X protein and cleaved poly (ADP‑ribose) polymerase. The results indicate that ZOL inhibited cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway and this anti‑leukemic activity appeared notably enhanced in HL‑60/A cells. As ZOL is already available for clinical use, these results indicate that it may be an effective addition to the chemotherapeutic strategies for AML.
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View References

1 

Focosi D: Acute myeloid leukaemia. Lancet. 369:3672007. View Article : Google Scholar : PubMed/NCBI

2 

Waller CF: Imatinib mesylate. Recent Results Cancer Res. 201:1–25. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Moreau P, Richardson PG, Cavo M, Orlowski RZ, San Miguel JF, Palumbo A and Harousseau JL: Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 120:947–959. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Kiper HD, Kaymaz B Tezcanli, Gokbulut AA, Selvi N, Avci CB, Kosova B, Iskender G, Yandim MK, Gunduz C, Sahin F, et al: STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells. Biomed Pharmacother. 67:527–532. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Jagdev SP, Coleman RE, Shipman CM, Rostami HA and Croucher PI: The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: Evidence for synergy with paclitaxel. Br J Cancer. 84:1126–1134. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Stresing V, Fournier PG, Bellahcéné A, Benzaïd I, Mönkkönen H, Colombel M, Ebetino FH, Castronovo V and Clézardin P: Nitrogen-containing bisphosphonates can inhibit angiogenesis in vivo without the involvement of farnesyl pyrophosphate synthase. Bone. 48:259–266. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Tassone P, Tagliaferri P, Viscomi C, Palmieri C, Caraglia M, D'Alessandro A, Galea E, Goel A, Abbruzzese A, Boland CR and Venuta S: Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro. Br J Cancer. 88:1971–1978. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Goffinet M, Thoulouzan M, Pradines A, Lajoie-Mazenc I, Weinbaum C, Faye JC and Séronie-Vivien S: Zoledronic acid treatment impairs protein geranyl-geranylation for biological effects in prostatic cells. BMC Cancer. 6:602006. View Article : Google Scholar : PubMed/NCBI

9 

Iguchi T, Miyakawa Y, Yamamoto K, Kizaki M and Ikeda Y: Nitrogen-containing bisphosphonates induce S-phase cell cycle arrest and apoptosis of myeloma cells by activating MAPK pathway and inhibiting mevalonate pathway. Cell Signal. 15:719–727. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Oades GM, Senaratne SG, Clarke IA, Kirby RS and Colston KW: Nitrogen containing bisphosphonates induce apoptosis and inhibit the mevalonate pathway, impairing Ras membrane localization in prostate cancer cells. J Urol. 170:246–252. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Kuroda J, Kimura S, Segawa H, Kobayashi Y, Yoshikawa T, Urasaki Y, Ueda T, Enjo F, Tokuda H, Ottmann OG and Maekawa T: The third-generation bisphosphonate Zoledronic Acid synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate. Blood. 102:2229–2235. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Fiegl M, Juergens M, Hiddemann W and Braess J: Cytotoxic activity of the third-generation bisphosphonate zoledronic acid in acute myeloid leukemia. Leuk Res. 31:531–539. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Ohtsuka Y, Manabe A, Kawasaki H, Hasegawa D, Zaike Y, Watanabe S, Tanizawa T, Nakahata T and Tsuji K: RAS-blocking bisphosphonate zoledronic acid inhibits the abnormal proliferation and differentiation of juvenile myelomonocytic leukemia cells in vitro. Blood. 106:3134–3141. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Chuah C, Barnes DJ, Kwok M, Corbin A, Deininger MW, Druker BJ and Melo JV: Zoledronate inhibits proliferation and induces apoptosis of imatinib-resistant chronic myeloid leukaemia cells. Leukemia. 19:1896–1904. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ebihara Y, Tsuji K, Lyman SD, Sui X, Yoshida M, Muraoka K, Yamada K, Tanaka R and Nakahata T: Synergistic action of Flt3 and gp130 signalings in human hematopoiesis. Blood. 90:4363–4368. 1997.PubMed/NCBI

16 

Hatzimichael E, Georgiou G, Benetatos L and Briasoulis E: Gene mutations and molecularly targeted therapies in acute myeloid leukemia. Am J Blood Res. 3:29–51. 2013.PubMed/NCBI

17 

Liu SS, Wang XP, Li XB, Liang JY, Liu LL, Lu Y, Zhong XY and Chen YX: Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest. Biomed Pharmacother. 68:1031–1036. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Wang L, Chen B, Lin M, Cao Y, Chen Y, Chen X, Liu T and Hu J: Decreased expression of nucleophosmin/B23 increases drug sensitivity of adriamycin-resistant Molt-4 leukemia cells through mdr-1 regulation and Akt/mTOR signaling. Immunobiology. 220:331–340. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Zhang B, Yang Y, Shi X, Liao W, Chen M, Cheng AS, Yan H, Fang C, Zhang S, Xu G, et al: Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-β/β-catenin signaling and epithelial-mesenchymal transition. Cancer Lett. 356:704–712. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Forsea AM, Müller C, Riebeling C, Orfanos CE and Geilen CC: Nitrogen-containing bisphosphonates inhibit cell cycle progression in human melanoma cells. Br J Cancer. 91:803–810. 2004.PubMed/NCBI

21 

Wong WW and Puthalakath H: Bcl-2 family proteins: The sentinels of the mitochondrial apoptosis pathway. IUBMB Life. 60:390–397. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Ottewell PD, Woodward JK, Lefley DV, Evans CA, Coleman RE, Holen I and Penelope D: Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone. Mol Cancer Ther. 8:2821–2832. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Fan RF, Chen YX, Fang ZG, Guo XY, Lu Y, Liu LL, Xu YC, Liu XF and Lin DJ: Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis. Mol Med Rep 14: 5660-5666, 2016.
APA
Fan, R., Chen, Y., Fang, Z., Guo, X., Lu, Y., Liu, L. ... Lin, D. (2016). Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis. Molecular Medicine Reports, 14, 5660-5666. https://doi.org/10.3892/mmr.2016.5957
MLA
Fan, R., Chen, Y., Fang, Z., Guo, X., Lu, Y., Liu, L., Xu, Y., Liu, X., Lin, D."Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis". Molecular Medicine Reports 14.6 (2016): 5660-5666.
Chicago
Fan, R., Chen, Y., Fang, Z., Guo, X., Lu, Y., Liu, L., Xu, Y., Liu, X., Lin, D."Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis". Molecular Medicine Reports 14, no. 6 (2016): 5660-5666. https://doi.org/10.3892/mmr.2016.5957
Copy and paste a formatted citation
x
Spandidos Publications style
Fan RF, Chen YX, Fang ZG, Guo XY, Lu Y, Liu LL, Xu YC, Liu XF and Lin DJ: Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis. Mol Med Rep 14: 5660-5666, 2016.
APA
Fan, R., Chen, Y., Fang, Z., Guo, X., Lu, Y., Liu, L. ... Lin, D. (2016). Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis. Molecular Medicine Reports, 14, 5660-5666. https://doi.org/10.3892/mmr.2016.5957
MLA
Fan, R., Chen, Y., Fang, Z., Guo, X., Lu, Y., Liu, L., Xu, Y., Liu, X., Lin, D."Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis". Molecular Medicine Reports 14.6 (2016): 5660-5666.
Chicago
Fan, R., Chen, Y., Fang, Z., Guo, X., Lu, Y., Liu, L., Xu, Y., Liu, X., Lin, D."Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells by promoting apoptosis". Molecular Medicine Reports 14, no. 6 (2016): 5660-5666. https://doi.org/10.3892/mmr.2016.5957
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