Bovine dialyzable leukocyte extract modulates AP-1 DNA-binding activity and nuclear transcription factor expression in MCF-7 breast cancer cells.

BACKGROUND: We have previously demonstrated that bovine dialyzable leukocyte extract (bDLE) induces death through an apoptosis mechanism in MCF-7 breast cancer cells. Depending on the cell type and stimulus, activating protein-1 (AP-1) has been shown to regulate cell proliferation and differentiation, the stress response, apoptosis and survival. It remains unknown whether AP-1 and other transcription factors are mechanisms by which bDLE induces cell death. METHODS: To determine whether bDLE modulates the AP-1 DNA binding and gene expression, MCF-7 breast cancer cells were treated with bDLE (0, 1, 5, 10 U) for 72 h and evaluated by electrophoretic mobility shift assay, reverse transcriptase-polymerase chain reaction and Western blot assays. RESULTS: bDLE induced inhibition of cell growth, suppressed the AP-1 DNA-binding activity, decreased c-Jun protein expression and modulated NFATx, NFATc, NFkappaB, c-Jun and c-Fos transcription factor gene expression in MCF-7 breast cancer cells. DISCUSSION: The present data indicate that bDLE can block the AP-1 DNA-binding activity and expression of several transcriptions factors in breast cancer cells, which will have great potential in improving cancer therapy.

IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients.

BACKGROUND: IMMUNEPOTENT CRP is a mixture of low molecular weight substances, some of which have been shown to be capable of modifying the immune response. We evaluated the response and adjuvant effect of IMMUNEPOTENT CRP on non-small cell lung cancer (NSCLC) patients in a phase I clinical trial. METHODS: Twenty-four NSCLC patients were included in the study and divided into two groups. Group 1 received a conventional treatment of 5400 cGy external radiotherapy in 28 fractions and chemotherapy consisting of intravenous cisplatin (40 mg/m(2)) delivered weekly for 6 weeks. Group 2 received the conventional treatment plus IMMUNEPOTENT CRP (5 U) administered daily. We performed clinical evaluation by CT scan and radiography analysis, and determined the quality of life of the patients with the Karnofsky performance scale. A complete blood count (red and white blood cell tests), including flow cytometry analysis, blood work (alkaline phosphatase test) and a delayed-type hypersensitivity (DTH) skin test for PPD, Varidase and Candida were performed. RESULTS: The administration of IMMUNEPOTENT CRP induced immunomodulatory activity (increasing the total leukocytes and T-lymphocyte subpopulations CD4(+), CD8(+), CD16(+) and CD56(+), and maintaining DHT) and increased the quality of the patients' lives, suggesting immunologic protection against chemotherapeutic side-effects in NSCLC patients. DISCUSSION: Our results suggest the possibility of using IMMUNEPOTENT CRP alongside radiation and chemotherapy for maintaining the immune system and increasing the quality of life of the patients.

Bovine dialyzable leukocyte extract modulates cytokines and nitric oxide production in lipopolysaccharide-stimulated human blood cells.

BACKGROUND: In the current study, we determined whether bovine dialyzable leukocyte extract (bDLE) modulates lipopolysaccharide (LPS)-induced nitric oxide and cytokine overproduction. METHODS: Human whole blood cells were treated with LPS (50 ng) + bDLE (1 U). RESULTS: The bDLE treatment decreased nitric oxide as well as TNF-alpha, IL-6 and IL-10 (P <0.01) cytokine production. In addition, it decreased TNF-alpha, IL-1beta and IL-6 mRNA expression and suppressed IL-10 and IL-12p40 mRNA expression, but did not modulate IL-8 mRNA expression in LPS-stimulated human blood cells. DISCUSSION: Our results suggest that bDLE may effectively modulate the fatal symptoms of hypotensive shock associated with endotoxin (LPS)-induced nitric oxide and cytokine production, and this may offer therapeutic potential for the treatment of endotoxic shock.