ABSTRACT
BACKGROUND: Noscapine has demonstrated potent antitumour activity and minimum toxicity in cancer models. Recently, noscapine has been shown to limit tumour growth and lymphatic metastasis of PC3 human prostate cancer mice. The prophylactic effects of noscapine are not known. MATERIALS AND METHODS: Nude mice received oral noscapine (300 mg/kg per day; 'treatment'; n=10) or diluent ('control'; n=10) for 56 days, beginning 7 days after inoculation with PC3 human prostate cancer cells; or noscapine for 70 days, beginning 7 days before inoculation ('pretreatment'; n=10). RESULTS: Mean total tumour volumes were 1731.6+/-602.0 mm(3) in the control group, 644.3+/-545.1 mm(3) in the noscapine pretreatment group and 910.9+/-501.1 mm(3) in the noscapine treatment group (p<0.001 pretreatment vs. control, p<0.05 pretreatment vs. control, p<0.001 pretreatment vs. treatment group), with no evidence of toxicity. Noscapine pretreatment and treatment also reduced tumour weight, the incidence of metastasis and primary tumour inhibition rate. CONCLUSION: Pretreatment with oral noscapine limited tumour growth and lymphatic metastasis of PC3 human prostate cancer in this mouse model and conferred a significant additional benefit over noscapine treatment in final tumour volume.
Subject(s)
Antitussive Agents/therapeutic use , Disease Models, Animal , Noscapine/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Animals , Cell Line, Tumor , Disease Progression , Humans , Lymphatic Metastasis , Male , Mice , Mice, Nude , Prostatic Neoplasms/secondary , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Noscapine, a non-toxic alkaloid and common constituent of cough medicine, stabilises tubulin. It inhibits the growth of several human and murine neoplasms, with no significant toxicity. Its effect on prostate cancer has not been evaluated. MATERIALS AND METHODS: Noscapine was administered orally (300 mg/kg per day) for 56 days to PC3 human prostate cancer-bearing immunodeficient mice (n=10). Immunodeficient control mice (n=10) received only diluent in an identical regimen. RESULTS: Mean total tumour weight was 0.42 +/- 0.23 g and 0.97 +/- 0.31 g (p<0.001) in the noscapine-treated group and the control group, respectively, without evidence of toxicity. Metastases occurred less frequently in the treatment than the control group (30% vs. 90%; p<0.05). CONCLUSION: Oral administration of noscapine limited tumour growth and lymphatic metastasis of PC3 human prostate cancer in this mouse model, supporting its therapeutic potential as a nontoxic and easily administered treatment for metastatic cancer.
Subject(s)
Noscapine/pharmacology , Prostatic Neoplasms/drug therapy , Animals , Body Weight/drug effects , Cell Growth Processes/drug effects , Cell Line, Tumor , Disease Progression , Humans , Male , Mice , Mice, Nude , Neoplasm Metastasis , Prostatic Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
Parathyroid hormone-related protein (PTHrP) is an oncoprotein that is expressed in many malignancies as well as normal tissues. At essentially every site of expression, PTHrP regulates cell growth and proliferation. We and other investigators have previously reported that PTHrP is widely expressed by prostate cancer. For this tumor, there are substantial in vitro and correlative data that PTHrP expression regulates the progression of the tumor, especially in bone, but little direct data. We studied the effects of PTHrP expression on prostate cancer behavior directly in a mouse model of human prostate cancer cells that were transfected to express different forms of the polypeptide and then injected intraskeletally. Skeletal progression of the prostate cancer cells was evaluated radiologically and by measurement of serum tumor markers. PTHrP transfection converted a non-invasive cell line into one that progressed in the skeleton: Injection of the PTHrP transfected cells resulted in greater tumor progression in bone when compared to non-transfected cells, and this effect was also influenced by non-amino terminal peptides of PTHrP. Serum measurements of PTHrP, IL-6, IL-8, and calcium reflected tumor burden. Our experiments provide direct in vivo evidence that PTHrP expression results in the skeletal progression of prostate cancer cells.
