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Antitumor effect of meclofenamic acid on human androgen-independent prostate cancer: a preclinical evaluation

  • Urology – Original Paper
  • Published:
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Abstract

Purpose

Prostate cancer is a worldwide public health problem and its treatment continues to be a therapeutic challenge especially in patients with metastatic androgen-independent cancer. Inflammation is a process that has been involved in the origin of this cancer and its inhibition has been postulated as a prophylactic and therapeutic strategy. The present study evaluated two non-steroidal anti-inflammatory drugs (meclofenamic acid and mefenamic acid) that have been studied very little in regard to cancer treatment.

Methods

In vitro, the cytotoxic effects of meclofenamic acid and mefenamic acid were determined in human prostate cancer cell lines (LNCaP: androgen-dependent; and PC3: androgen-independent). In vivo trials were divided into two phases; meclofenamic acid toxicity was initially determined at different doses (0, 5, 10 and 20 mg/kg/day/25 days) in BALB/c mice, after which a trial using non-toxic doses was carried out to evaluate the antitumor efficacy of the drug in a PC3/nude-mouse model of human androgen-independent prostate cancer.

Results

In vitro trials showed that only meclofenamic acid is highly cytotoxic in neoplastic prostate cells. The 5 and 10 mg/kg/day/25 day doses did not cause relevant toxicity in the BALB/c mouse trial, and so both doses were used in the nude-mouse model of cancer trial. This latter trial showed that meclofenamic acid significantly reduces tumor growth, prolongs survival, and is even capable of generating total tumor regression in up to 25% of mice treated at high dose.

Conclusions

Meclofenamic acid was shown to be a potential antineoplastic agent for both androgen-dependent and androgen-independent prostate cancer.

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Acknowledgments

This study was funded by the Fondo Ramon Alvarez Buylla de Aldana (Universidad de Colima) and the Fondo Mixto CONACYT-Gobierno de Colima, 2008-C01-83189.

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Authors and Affiliations

  1. School of Medicine, University of Colima., Av. Universidad 333, Colonia Las Víboras, 28040, Colima, Col., Mexico

    Alejandro D. Soriano-Hernández, Hector R. Galvan-Salazar, Daniel A. Montes-Galindo, Alejandrina Rodriguez-Hernandez, Rafael Martinez-Martinez, Jose Guzman-Esquivel, Luz M. Baltazar-Rodriguez, Francisco Espinoza-Gómez & Ivan Delgado-Enciso

  2. Hospital General de Zona Nº1 del IMSS, Av. De los Maestros 149, Colonia Centro, 28000, Colima, Mexico

    Jose Guzman-Esquivel

  3. Chemical Sciences School, University of Colima, Kilómetro 9 carretera Colima-Coquimatlán, 28400, Colima, México

    Laura L. Valdez-Velazquez

  4. Department of Biochemistry and Molecular Medicine, School of Medicine, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Av. Madero y Dr. Aguirre Pequeño, Colonia Mitras Centro, 64460, Monterrey, Nuevo León, Mexico

    Augusto Rojas-Martinez & Rocio Ortiz-Lopez

  5. Departamento de Ciencias Básicas. Escuela de Ingeniería, Arquitectura y Salud Instituto Tecnológico y de Estudios Superiores de Monterrey campus Guadalajara, Av. General Ramón Corona 2514, colonia Nuevo México, 45201, Zapopan, Jal., Mexico

    Rafael Gonzalez-Alvarez

  6. Instituto Estatal de Cancerología, Secretaria de Salud del Estado de Colima, Av. Liceo de Varones y Doctor Rubén Agüero, colonia La Esperanza, Colima, Mexico

    Ivan Delgado-Enciso

Authors
  1. Alejandro D. Soriano-Hernández
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  2. Hector R. Galvan-Salazar
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  3. Daniel A. Montes-Galindo
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  4. Alejandrina Rodriguez-Hernandez
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  5. Rafael Martinez-Martinez
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  6. Jose Guzman-Esquivel
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  7. Laura L. Valdez-Velazquez
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  8. Luz M. Baltazar-Rodriguez
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  9. Francisco Espinoza-Gómez
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  10. Augusto Rojas-Martinez
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  11. Rocio Ortiz-Lopez
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  12. Rafael Gonzalez-Alvarez
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  13. Ivan Delgado-Enciso
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Corresponding author

Correspondence to Ivan Delgado-Enciso.

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Soriano-Hernández, A.D., Galvan-Salazar, H.R., Montes-Galindo, D.A. et al. Antitumor effect of meclofenamic acid on human androgen-independent prostate cancer: a preclinical evaluation. Int Urol Nephrol 44, 471–477 (2012). https://doi.org/10.1007/s11255-011-0012-0

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  • DOI: https://doi.org/10.1007/s11255-011-0012-0

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