Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of various neuropeptides present in the prostate, including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. These results indicate that both GRP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response.
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PMID:Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells. 992 57

Neutral endopeptidase 24.11 (NEP) is a 90-110 kDa cell surface cell surface peptidase that is normally expressed by numerous tissues, including prostate, kidney, intestine, endometrium, adrenal glands and lung. This enzyme cleaves peptide bonds on the amino side of hydrophobic amino acids and inactivates a variety of physiologically active peptides, including atrial natriuretic factor, substance P, bradykinin, oxytocin, Leu- and Met-enkephalins, neurotensin, bombesin, endothelin-1, and bombesin-like peptides. NEP reduces the local concentration of peptide available for receptor binding and signal transduction. Loss or decreases in NEP expression have been reported in a variety of malignancies. Reduced NEP may promote peptide-mediated proliferation by allowing accumulation of higher peptide concentrations at the cell surface, and facilitate the development or progression of neoplasia. We have used prostate cancer as model in which to study the involvement of NEP in malignancy. Using a variety of experimental approaches, including recombinant NEP, cell lines expressing wild-type and mutant NEP protein, and cell lines expressing NEP protein with a mutated cytoplasmic domain, we have examined the effects of NEP on cell migration and cell survival. We have shown that the effects of NEP are mediated by its ability to catalytically inactivate substrates such as bombesin and endothelin-1, but also through direct protein-protein interaction with other protein such as Lyn kinase [which associates with the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in NEP-Lyn-PI3-K protein complex], ezrin/radixin/moesin (ERM) proteins, and the PTEN tumor suppressor protein. We review the mechanisms of NEP's tumor suppressive action and how NEP loss contributes to tumor progression.
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PMID:Involvement of neutral endopeptidase in neoplastic progression. 1605 17

One minute downward pressure on the tip of any one of the front 3 teeth (1st incisor, 2nd incisor, and canine) at the right and left sides of the upper and lower jaw by a wooden toothpick induced temporary disappearance (20 min approximately 4 hours) of abnormally increased pain parameters (pain grading, Substance P, & TXB2), and cancer parameters (Telomere, Integrin alpha5beta1, Oncogene C-fos Ab2, etc. of Astrocytoma, Glioblastoma, squamous cell carcinoma of esophagus, adenocarcinoma of lung, breast cancer, adenocarcinoma of colon, prostate cancer). The effect included temporary disappearance of headache, toothache, chest and abdominal pain, and backache, often with improved memory & concentration. Since these beneficial changes resembled the effects of giving one optimal dose of DHEA, increase of DHEA was measured. Above mechanical stimulation of one of these front teeth increased abnormally reduced DHEA levels of less than 10 ng to norm1 100 approximately 130 ng BDORT units and normal cell (NC) telomeres from markedly reduced values to near normal values, and improved acetylcholine in the Hippocampus. Large organ representation areas for the Adrenal gland & Hippocampus may exist at these front teeth. This method can be used for emergency pain control and can explain the beneficial effect of bruxism and tooth brushing, through the increase of DHEA levels and activities of the Hippocampus by increasing Acetylcholine. Increasing NC telomere to optimally high level resulted in disappearance of pain and improvement or significant reduction of malignant tumor. Repeated daily press needle stimulation of True ST. 36 increased NC telomere 450-700 ng BDORT units. One optimal dose of DHEA increased NC telomere 525 ng DBORT units and eliminated the pain and abnormally increased cancer parameters; effect of one optimal dose lasted 0.5-11 months. One optimal dose of Boswellia Serrata or Astragalus not only increased NC telomere 650 ng BDORT units, eliminating pain and cancer parameters, but also reduced the size of the Astrocytoma grade I by 10-20% and the Glioblastoma by 15-90% in less than 2-6 months in some patients, as long as high NC telomere is maintained.
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PMID:Temporary anti-cancer & anti-pain effects of mechanical stimulation of any one of 3 front teeth (1st incisor, 2nd incisor, & canine) of right & left side of upper & lower jaws and their possible mechanism, & relatively long term disappearance of pain & cancer parameters by one optimal dose of DHEA, Astragalus, Boswellia Serrata, often with press needle stimulation of True ST. 36. 2034 85

Neuropeptides may be essential to the growth and progress of prostate cancer, particularly during androgen-independent cell development. To determine whether neuropeptide antagonists substance P analogues can be used as therapeutic agents in the treatment of prostate cancer, their effects on the growth and invasiveness of established human prostate cancer cell lines were examined. The effects of [d-Arg(1), d-phe(5), d-Trp(7,9), Leu(11)]substance P and [Arg(6), d-Trp(7,9), MePhe(8)]substance P(6-11) on two androgen-independent cell lines (PC-3 and DU-145) and an androgen-dependent cell line (LNCaP) were studied. The cytotoxicity of substance P analogues was assessed based on their effects on DNA synthesis and cell proliferation by [(3)H]thymidine incorporation and cell growth assays, respectively. Inhibition of the invasiveness of prostate cancer cells was estimated based on the extent of cell penetration of reconstituted basement membrane. Substance P analogues inhibited DNA synthesis and cell proliferation of prostate cancer cells dose dependently but complete recovery was achieved by the addition of bombesin or substance P. [d-Arg(1), d-phe, d-Trp(7,9), Leu(11)]substance P inhibited the invasiveness of PC-3 cells. Neuropeptide antagonists substance P analogues have been found useful as therapeutic agents for prostate cancer. Their action occurs primarily through the inhibition of Ca(2+) mobilizing neuropeptides such as bombesin and substance P.
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PMID:Suppression of the growth and invasiveness of human prostate cancer cells in vitro by neuropeptide antagonist substance P analogues. 2122 66

NK1 is a tachykinin receptor highly relevant to tumorigenesis and metastasis development in breast cancer and other carcinomas. Despite the substantial efforts done to develop potent NK1 receptor antagonists, none of these antagonists had shown good antitumor activity in clinical trials. Now, we have tested the effect of inhibition of the neuropeptide Substance P (SP), a NK1 ligand, as a potential therapeutic approach in cancer. We found that the inhibition of SP with antibodies strongly inhibit cell growth and induce apoptosis in breast, colon, and prostate cancer cell lines. These effects were accompained by a decrease in the mitogen-activated kinase singaling pathway. Interestingly, in some cell lines SP abrogation decreased the steady state of Her2 and EGFR, suggesting that SP-mediated signaling is important for the basal activity of these ErbB receptors. In consequence, we observed a blockade of the cell cycle progression and the inhibition of several cell cycle-related proteins including mTOR. SP inhibition also induced cell death in cell lines resistant to Lapatinib and Trastuzumab that have increased levels of active Her2, suggesting that this therapeutic approach could be also effective for those cancers resistant to current anti-ErbB therapies. Thus, we propose a new therapeutic strategy for those cancers that express NK1 receptor and/or other tachykinin receptors, based in the immuno-blockade of the neuropeptide SP.
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PMID:Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. 2160 73