ABSTRACT
Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.
Subject(s)
Antineoplastic Agents/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Meclofenamic Acid/pharmacology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Fibrosis , Humans , Immunohistochemistry , Male , Mice, Nude , Neoplasm Invasiveness , Neovascularization, Pathologic/drug therapy , Prostate/drug effects , Prostate/pathology , Prostatic Neoplasms, Castration-Resistant/chemistry , Reproducibility of ResultsABSTRACT
ABSTRACT Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.
Subject(s)
Animals , Humans , Male , Antineoplastic Agents/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Meclofenamic Acid/pharmacology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Fibrosis , Immunohistochemistry , Mice, Nude , Neoplasm Invasiveness , Neovascularization, Pathologic/drug therapy , Prostate/drug effects , Prostate/pathology , Prostatic Neoplasms, Castration-Resistant/chemistry , Reproducibility of ResultsABSTRACT
INTRODUCTION: A high-fat diet and male obesity are aspects associated with germinal epithelial alterations and male infertility. Some reports have shown that certain tetracyclines can protect the germinal epithelium from toxic drugs. The aim of the present study design was to evaluate the possible effect of doxycycline on testicular germ cells in individuals fed a Western diet (atherogenic), using a murine model. METHODS: Two groups of male mice (BALB/c) were fed a high-fat Western diet (HFD). One of these two groups was given doxycycline at a dose of 10 mg/kg/day (HFD+Dox). A third group was fed a standard rodent diet (SD group). After 6 months, the mice were euthanized and morphologic and histopathologic analyses were performed. RESULTS: Germinal epithelial height was similar between the SD group (54 µm) and the HFD+Dox group (53 µm) (p = 0.26), and it was significantly reduced in the HFD group (47 µm) (p = 0.0001). The degree of germinal epithelial loss (DGEL) was significantly lower in the SD (10) and HFD+Dox (12.5) groups than in the HFD group (30) (p = 0.0001 and =0.007, respectively). There were no differences in the DGEL between the SD and HFD+Dox groups (p = 0.42). CONCLUSIONS: Doxycycline administration was shown to prevent germinal epithelial loss in the testes of mice fed a high-fat diet. Future studies are necessary to evaluate the clinical usefulness of doxycycline or its analogs in persons with a habitual high-fat diet.
Subject(s)
Anti-Bacterial Agents/pharmacology , Doxycycline/pharmacology , Epithelium/drug effects , Epithelium/pathology , Testis/drug effects , Testis/pathology , Adiposity , Animals , Diet, Atherogenic , Epididymis/pathology , Germ Cells/drug effects , Male , Mice , Mice, Inbred BALB C , Organ SizeABSTRACT
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.