Cancer Chemotherapy and Pharmacology

, Volume 61, Issue 5, pp 809–817 | Cite as

Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice

  • Daniele Martarelli
  • Pierluigi Pompei
  • Caterina Baldi
  • Giovanni Mazzoni
Original Article

Abstract

Adrenocortical carcinoma is a rare tumor of the adrenal gland which requires new therapeutic approaches as its early diagnosis is difficult and prognosis poor despite therapies used. Recently, mebendazole has been proved to be effective against different cancers. The aim of our study was to evaluate whether mebendazole may result therapeutically useful in the treatment of human adrenocortical carcinoma. We analyzed the effect of mebendazole on human adrenocortical carcinoma cells in vitro and after implantation in nude mice. In order to clarify mechanisms of mebendazole action, metastases formation, apoptosis and angiogenesis were also investigated. Mebendazole significantly inhibited cancer cells growth, both in vitro and in vivo, the effects being due to the induction of apoptosis. Moreover, mebendazole inhibited invasion and migration of cancer cells in vitro, and metastases formation in vivo. Overall, these data suggest that treatment with mebendazole, also in combination with standard therapies, could provide a new protocol for the inhibition of adrenocortical carcinoma growth.

Keywords

Adrenocortical carcinoma Mebendazole Nude mice Chemotherapy 

References

  1. 1.
    Ammann RW, Ilitsch N, Marincek B, Freiburghaus AU (1994) Effect of chemotherapy on the larval mass and the long-term course of alveolar echinococcosis. Swiss Echinococcosis Study Group. Hepatology 19:735–742PubMedCrossRefGoogle Scholar
  2. 2.
    Berruti A, Terzolo M, Sperone P, Pia A, Casa SD, Gross DJ, Carnaghi C, Casali P, Porpiglia F, Mantero F, Reimondo G, Angeli A, Dogliotti L (2005) Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer 12:657–666PubMedCrossRefGoogle Scholar
  3. 3.
    Davis PD, Dougherty GJ, Blakey DC, Galbraith SM, Tozer GM, Holder AL, Naylor MA, Nolan J, Stratford MR, Chaplin DJ, Hill SA (2002) ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature. Cancer Res 62:7247–7253PubMedGoogle Scholar
  4. 4.
    Dayan AD (2003) Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropic 86:141–159CrossRefGoogle Scholar
  5. 5.
    Fogh J, Fogh JM, Orfeo T (1977) One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 59:221–226PubMedGoogle Scholar
  6. 6.
    Gazdar A, Oie H, Shackleton C, Chen T, Triche T, Myers C, Chrousos G, Brennan M, Stein C, La Rocca R (1990) Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis. Cancer Res 50:5488–5496PubMedGoogle Scholar
  7. 7.
    Gee MS, Makonnen S, al-Kofahi K, Roysam B, Payvandi F, Man HW, Muller GW, Lee WM (2003) Selective cytokine inhibitory drugs with enhanced antiangiogenic activity control tumor growth through vascular inhibition. Cancer Res 63:8073–8078PubMedGoogle Scholar
  8. 8.
    Gicquel C, Raffin-Sanson M, Gaston V, Bertagna X, Plouin P, Schlumberger M, Louvel A, Luton J, Le Bouc Y (1997) Structural and functional abnormalities at 11 p 15 are associated with the malignant phenotype in sporadic adrenocortical tumors. Study on a series of 82 tumors. J Clin Endocrinol Metab 82:2559–2565PubMedCrossRefGoogle Scholar
  9. 9.
    Jordan MA, Thrower D, Wilson L (1991) Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 51:2212–2222PubMedGoogle Scholar
  10. 10.
    Leibovitz A, McCombs WM, Johnston D, McCoy CE, Stinson JC (1973) New human cancer cell culture lines. I. SW-13, small-cell carcinoma of the adrenal cortex. J Natl Cancer Inst 51:691–697PubMedGoogle Scholar
  11. 11.
    Logie A, Boudou P, Boccon-Gibod L, Baudin E, Vassal G, Schlumberger M, Le Bouc Y, Gicquel C (2000) Establishment and characterization of a human adrenocortical carcinoma xenograft model. Endocrinology 141:3165–3171PubMedCrossRefGoogle Scholar
  12. 12.
    Mukhopadhyay T, Sasaki J, Ramesh R, Roth JA (2002) Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo. Clin Cancer Res 8:2963–2969PubMedGoogle Scholar
  13. 13.
    Muller E, Akovbiantz A, Ammann RW, Bircher J, Eckert J, Wisslerm K, Witassek F, Wuthrich B (1982) Treatment of human echinococcosis with mebendazole. Preliminary observations in 28 patients. Hepatogastroenterology 29:236–239PubMedGoogle Scholar
  14. 14.
    Norton JA (2005) Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1528–1539Google Scholar
  15. 15.
    Rainey W, Bird I, Mason J (1994) NCI-H295 cell line: a pluripotent model for human adrenocortical studies. Mol Cell Endocrinol 100:45–50PubMedCrossRefGoogle Scholar
  16. 16.
    Sasaki J, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T (2002) The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. Mol Cancer Ther 1:1201–1209PubMedGoogle Scholar
  17. 17.
    Tuxhorn JA, McAlhany SJ, Dang TD, Ayala GE, Rowley DR (2002) Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res 62:3298–3307PubMedGoogle Scholar
  18. 18.
    Wooten MD, King DK (1993) Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 72:3145–3155PubMedCrossRefGoogle Scholar
  19. 19.
    Young SL, Chaplin DJ (2004) Combretastatin A4 phosphate: background and current clinical status. Expert Opin Invest Drugs 13:1171–1182CrossRefGoogle Scholar
  20. 20.
    Zhiheng H, Bateman A (1999) Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res 59:3222–3229Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Daniele Martarelli
    • 1
  • Pierluigi Pompei
    • 1
  • Caterina Baldi
    • 1
  • Giovanni Mazzoni
    • 1
  1. 1.Department of Experimental Medicine and Public HealthUniversity of CamerinoCamerino (Macerata)Italy

Personalised recommendations