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

• Published in: International urology and nephrology Vol. 44; no. 2; pp. 471 - 477
• Main Authors: Soriano-Hernández, Alejandro D., Galvan-Salazar, Hector R., Montes-Galindo, Daniel A., Rodriguez-Hernandez, Alejandrina, Martinez-Martinez, Rafael, Guzman-Esquivel, Jose, Valdez-Velazquez, Laura L., Baltazar-Rodriguez, Luz M., Espinoza-Gómez, Francisco, Rojas-Martinez, Augusto, Ortiz-Lopez, Rocio, Gonzalez-Alvarez, Rafael, Delgado-Enciso, Ivan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-04-2012; Springer Nature B.V
• Subjects: Androgens - therapeutic use; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Disease Progression; Dose-Response Relationship, Drug; Humans; Male; Meclofenamic Acid - administration & dosage; Meclofenamic Acid - therapeutic use; Medicine; Medicine & Public Health; Mice; Mice, Nude; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Nephrology; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Treatment Outcome; Tumor Cells, Cultured; Urology; Urology – Original Paper; Fenamates; Anti-inflammatory agent; Prostatic neoplasms; Meclofenamic acid; Therapeutics
• ISSN: 0301-1623; 1573-2584
• DOI: 10.1007/s11255-011-0012-0

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.