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Arsenic trioxide: expanding roles for an ancient drug?

Leukemia volume 18, pages 1457–1459 (2004)Cite this article

In this issue, Rousselot et al1 describe their experience using two different arsenicals in the treatment of 12 patients with advanced multiple myeloma. Application of heavy metals such as platinum compounds in the treatment of cancer is well established. The use of arsenicals as therapeutic agents in medicine dates back more than 2400 years to ancient Greece and Rome.2 In the 19th century, potassium arsenite, in the form of Fowler's solution, was used to treat a number of ailments.3 More recently, Paul Ehrlich used an organic arsenical, salvarsan, to treat syphilis and trypanosomiasis.4, 5 The use of arsenic in treating leukemia was first described in the 19th century,6 and a report from Boston University in 1931 further suggested activity in chronic myelogenous leukemia7 Investigators from China demonstrated the efficacy of arsenic trioxide in treating patients with relapsed acute promyelocytic leukemia (APL),8 and this was further confirmed by studies conducted in the US.9, 10

Although the precise mechanism of action of arsenic trioxide in APL is not clear, a number of in vitro studies have contributed to the understanding of possible mechanisms by which arsenic therapy leads to induction of apoptosis, inhibition of growth and angiogenesis, modulation of cellular signaling pathways, perturbation of cellular redox status, and promotion of differentiation.11 Furthermore, the demonstration that arsenical compounds could induce apoptosis in myeloid leukemia cell lines independent of the expression of PML and PML-RARα proteins has led to evaluation of this agent in other neoplasms.12

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References

  1. Rousselot P, Larghero J, Arnulf B, Poupon J, Royer B, Tibi A et al. A clinical and pharmacological study of arsenic trioxide in advanced multiple myeloma patients. Leukemia, 22 July 2004 [Epub ahead of print].

  2. Klaassen CD . Heavy metals and heavy-metal antagonists. In: Hardman JG, Gilman AG, Limbird LE, (eds). The Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 1996, pp 1649–1672.

    Google Scholar 

  3. Haller JS . Therapeutic mule: the use of arsenic in the nineteenth century materia medica. Pharm Hist 1975; 17: 87–100.

    CAS  PubMed  Google Scholar 

  4. Kwong YL, Todd D . Delicious poison: arsenic trioxide for the treatment of leukemia. Blood 1997; 89: 3487–3488.

    CAS  PubMed  Google Scholar 

  5. Aronson SM . Arsenic and old myths. R I Med 1994; 77: 233–234.

    CAS  PubMed  Google Scholar 

  6. Cutler EG, Bradford EH . Action of iron, cod-liver oil, and arsenic on the globular richness of blood. Am J Med Sci 1878; 75: 74–84.

    Article  Google Scholar 

  7. Forkner CE, Scott TFM . Arsenic as a therapeutic agent in chronic myelogenous leukemia. JAMA 1931; 97: 3–5.

    Article  Google Scholar 

  8. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997; 89: 3354–3360.

    CAS  PubMed  Google Scholar 

  9. Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 1998; 339: 1341–1348.

    Article  CAS  PubMed  Google Scholar 

  10. Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 2001; 19: 3852–3860.

    Article  CAS  PubMed  Google Scholar 

  11. Miller Jr WH, Schipper HM, Lee JS, Singer J, Waxman S . Mechanisms of action of arsenic trioxide. Cancer Res 2002; 62: 3893–3903.

    CAS  PubMed  Google Scholar 

  12. Novick SC, Warrell Jr RP . Arsenicals in hematologic cancers. Semin Oncol 2000; 27: 495–501.

    CAS  PubMed  Google Scholar 

  13. Park WH, Seol JG, Kim ES, Hyun JM, Jung CW, Lee CC et al. Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res 2000; 60: 3065–3071.

    CAS  PubMed  Google Scholar 

  14. Rousselot P, Labaume S, Marolleau JP, Larghero J, Noguera MH, Brouet JC et al. Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in plasma cells from myeloma patients. Cancer Res 1999; 59: 1041–1048.

    CAS  PubMed  Google Scholar 

  15. Hayashi T, Hideshima T, Akiyama M, Richardson P, Schlossman RL, Chauhan D et al. Arsenic trioxide inhibits growth of human multiple myeloma cells in the bone marrow microenvironment. Mol Cancer Ther 2002; 1: 851–860.

    CAS  PubMed  Google Scholar 

  16. Liu Q, Hilsenbeck S, Gazitt Y . Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood 2003; 101: 4078–4087.

    Article  CAS  PubMed  Google Scholar 

  17. Munshi NC, Tricot G, Desikan R, Badros A, Zangari M, Toor A et al. Clinical activity of arsenic trioxide for the treatment of multiple myeloma. Leukemia 2002; 16: 1835–1837.

    Article  CAS  PubMed  Google Scholar 

  18. Hussein MA, Saleh M, Ravandi F, Mason J, Rifkin R, Ellison R . Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma. Br J Haematol 2004; 125: 470–476.

    Article  CAS  PubMed  Google Scholar 

  19. Grad JM, Bahlis NJ, Reis I, Oshiro MM, Dalton WS, Boise LH . Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Blood 2001; 98: 805–813.

    Article  CAS  PubMed  Google Scholar 

  20. Bahlis NJ, McCafferty-Grad J, Jordan-McMurry I, Neil J, Reis I, Kharfan-Dabaja M et al. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res 2002; 8: 3658–3668.

    CAS  PubMed  Google Scholar 

  21. Borad M, Swift RA, Sadler K, Yang H, Berenson JR . Melphalan, arsenic trioxide and ascorbic acid (MAC) is effective in the treatment of refractory and relapsed multiple myeloma (MM). Blood 2003; 102: 235a.

    Google Scholar 

  22. Birch R, Schwartzberg LS, Lawrence V, Schnell FM, Tongol JM, Prill SJ et al. A phase II study of arsenic trioxide (ATO) in combination with dexamethasone (Dex) and ascorbic acid (VITC) in patients with relapsed/refractory multiple myeloma. Blood 2003; 102: 386b.

    Google Scholar 

  23. Au WY, Kumana CR, Kou M, Mak R, Chan GC, Lam CW et al. Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia. Blood 2003; 102: 407–408.

    Article  CAS  PubMed  Google Scholar 

  24. Lu DP, Qiu JY, Jiang B, Wang Q, Liu KY, Liu YR et al. Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report. Blood 2002; 99: 3136–3143.

    Article  CAS  PubMed  Google Scholar 

  25. Duzkale H, Jilani I, Orsolic N, Zingaro RA, Golemovic M, Giles FJ et al. In vitro activity of dimethylarsinic acid against human leukemia and multiple myeloma cell lines. Cancer Chemother Pharmacol 2003; 51: 427–432.

    CAS  PubMed  Google Scholar 

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  1. Department of Leukemia, University of Texas – MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA

    F Ravandi

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Ravandi, F. Arsenic trioxide: expanding roles for an ancient drug?. Leukemia 18, 1457–1459 (2004). https://doi.org/10.1038/sj.leu.2403419

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