scholarly journals Peptide Receptor Targeting in Cancer: The Somatostatin Paradigm

2013 ◽  
Vol 2013 ◽  
pp. 1-20 ◽  
Author(s):  
Federica Barbieri ◽  
Adriana Bajetto ◽  
Alessandra Pattarozzi ◽  
Monica Gatti ◽  
Roberto Würth ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Antitumor Agents ◽  
Exocrine Secretion ◽  
Receptor Subtypes ◽  
Functional Roles ◽  
Cancer Types ◽  
Receptor Biology ◽  
G Protein Coupled

Peptide receptors involved in pathophysiological processes represent promising therapeutic targets. Neuropeptide somatostatin (SST) is produced by specialized cells in a large number of human organs and tissues. SST primarily acts as inhibitor of endocrine and exocrine secretion via the activation of five G-protein-coupled receptors, named sst1–5, while in central nervous system, SST acts as a neurotransmitter/neuromodulator, regulating locomotory and cognitive functions. Critical points of SST/SST receptor biology, such as signaling pathways of individual receptor subtypes, homo- and heterodimerization, trafficking, and cross-talk with growth factor receptors, have been extensively studied, although functions associated with several pathological conditions, including cancer, are still not completely unraveled. Importantly, SST exerts antiproliferative and antiangiogenic effects on cancer cells in vitro, and on experimental tumors in vivo. Moreover, SST agonists are clinically effective as antitumor agents for pituitary adenomas and gastro-pancreatic neuroendocrine tumors. However, SST receptors being expressed by tumor cells of various tumor histotypes, their pharmacological use is potentially extendible to other cancer types, although to date no significant results have been obtained. In this paper the most recent findings on the expression and functional roles of SST and SST receptors in tumor cells are discussed.

[10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDAMB- 231 Breast Tumor Cells

2019 ◽  
Vol 19 (5) ◽  
pp. 645-654 ◽  
Author(s):  
Angelina M. Fuzer ◽  
Ana C.B.M. Martin ◽  
Amanda B. Becceneri ◽  
James A. da Silva ◽  
Paulo C. Vieira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Antitumor Agents ◽  
Apoptotic Cell ◽  
3D Culture ◽  
Primary Concern ◽  
Breast Cancers ◽  
Her2 Gene

Background: Triple Negative Breast Cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of Estrogen (ER) and Progesterone Receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene, imposing difficulties to treatment. Interactions between tumor cells and their microenvironment facilitate tumor cell invasion in the surrounding tissues, intravasation through newly formed vessels, and dissemination to form metastasis. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in natural antitumor agents. In a previous work, we have demonstrated that [10]-gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including lung, bone and brain, in spontaneous and experimental in vivo metastasis assays in mouse model. Objective: This work aims to investigate the in vitro effects of [10]-gingerol, using human MDA-MB-231TNBC cells, in comparison to non-tumor MCF-10A breast cells, in order to understand the antitumor and antimetastatic effects found in vivo and in a 3D environment. Methods: We investigated different steps of the metastatic process in vitro, such as cell migration, invasion, adhesion and MMP activity. In addition, we analyzed the anti-apoptotic and genotoxic effects of [10]-gingerol using PEAnnexin, DNA fragmentation, TUNEL and comet assays, respectively. Results: [10]-gingerol was able to inhibit cell adhesion, migration, invasion and to induce apoptosis more effectively in TNBC cells, when compared to non-tumor cells, demonstrating that these mechanisms can be involved in the antitumor and antimetastatic effects of [10]-gingerol, found both in 3D culture and in vivo. Conclusion: Taken together, results found here are complementary to previous studies of our group and others and demonstrate that additional mechanisms, besides apoptotic cell death, is used by [10]-gingerol to accomplish its antitumor and antimetastatic effects. Our results indicate a potential for this natural compound as an antitumor molecule or as an adjuvant for chemotherapeutics already used in the clinic.

scholarly journals Molecular mechanisms of somatostatin receptor trafficking

2011 ◽  
Vol 48 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
Zsolt Csaba ◽  
Stéphane Peineau ◽  
Pascal Dournaud
Keyword(s):  
Molecular Mechanisms ◽  
Somatostatin Receptor ◽  
Cell Types ◽  
Exocrine Secretion ◽  
Receptor Subtypes ◽  
Hydrophobic Core ◽  
Somatostatin Receptor Subtypes ◽  
C Terminus

The neuropeptide somatostatin (SRIF) is an important modulator of neurotransmission in the central nervous system and acts as a potent inhibitor of hormone and exocrine secretion. In addition, SRIF regulates cell proliferation in normal and tumorous tissues. The six somatostatin receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, and sst5), which belong to the G protein-coupled receptor (GPCR) family, share a common molecular topology: a hydrophobic core of seven transmembrane-spanning α-helices, three intracellular loops, three extracellular loops, an amino-terminus outside the cell, and a carboxyl-terminus inside the cell. For most of the GPCRs, intracytosolic sequences, and more particularly the C-terminus, are believed to interact with proteins that are mandatory for either exporting neosynthesized receptor, anchoring receptor at the plasma membrane, internalization, recycling, or degradation after ligand binding. Accordingly, most of the SRIF receptors can traffic not onlyin vitrowithin different cell types but alsoin vivo. A picture of the pathways and proteins involved in these processes is beginning to emerge.

scholarly journals Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

2010 ◽  
Vol 299 (5) ◽  
pp. H1494-H1504 ◽  
Author(s):  
Gengqian Zhang ◽  
Sulei Xu ◽  
Yan Qian ◽  
Pingnian He
Keyword(s):  
Barrier Function ◽  
Protective Action ◽  
Platelet Activating Factor ◽  
Receptor Subtypes ◽  
Functional Roles ◽  
Sphingosine 1 Phosphate ◽  
Microvessel Permeability ◽  
Permeability Increase

Sphingosine-1-phosphate (S1P) has been demonstrated to enhance endothelial barrier function in vivo and in vitro. However, different S1P receptor subtypes have been indicated to play different or even opposing roles in the regulation of vascular barrier function. This study aims to differentiate the roles of endogenous endothelial S1P subtype receptors in the regulation of permeability in intact microvessels using specific receptor agonist and antagonists. Microvessel permeability was measured with hydraulic conductivity ( Lp) in individually perfused rat mesenteric venules. S1P-mediated changes in endothelial intracellular Ca2+ concentration ([Ca2+]i) was measured in fura-2-loaded venules. Confocal images of fluorescent immunostaining illustrated the spatial expressions of three S1P subtype receptors (S1PR1–3) in rat venules. The application of S1P (1 μM) in the presence of S1PR1–3 inhibited platelet-activating factor- or bradykinin-induced permeability increase. This S1P effect was reversed only with a selective S1PR1 antagonist, W-146, and was not affected by S1PR2 or S1PR3 antagonists JTE-013 and CAY-10444, respectively. S1PR1 was also identified as the sole receptor responsible for S1P-mediated increases in endothelial [Ca2+]i. S1PR2 or S1PR3 antagonist alone affected neither basal Lp nor platelet-activating factor-induced permeability increase. The selective S1PR1 agonist, SEW-2871, showed similar [Ca2+]i and permeability effect to that of S1P. These results indicate that, despite the presence of S1PR1–3 in the intact venules, only the activation of endothelial S1PR1 is responsible for the protective action of S1P on microvessel permeability and that endogenous S1PR2 or S1PR3 did not exhibit functional roles in the regulation of permeability under basal or acutely stimulated conditions.

Natural Product Gossypol and its Derivatives in Precision Cancer Medicine

2019 ◽  
Vol 26 (10) ◽  
pp. 1849-1873 ◽  
Author(s):  
Yun Zeng ◽  
Jingwen Ma ◽  
Liang Xu ◽  
Daocheng Wu
Keyword(s):  
Natural Product ◽  
Antitumor Agents ◽  
Synergistic Effects ◽  
Antitumor Agent ◽  
Current Status ◽  
Antitumor Effects ◽  
Cycle Arrest ◽  
Cancer Types

Gossypol, a natural product extracted from the seed, roots, and stem of cotton, was initially used as a male contraceptive but was subsequently investigated as a novel antitumor agent. This review depicts the current status of gossypol and its derivatives as novel antitumor agents as well as presents their preparation and characteristics, especially of some gossypol Schiff bases, through quantitative and structural analysis. The main attractive target sites of gossypol and its derivatives are Bcl-2 family proteins containing the anti-apoptosis proteins Bcl-2 and Bcl-XL. The molecular mechanism of gossypol analogs not only involves cell apoptosis but also autophagy, cell cycle arrest, and other abnormal cellular phenomena. Gossypol and its derivatives exert antitumor effects on different cancer types in vitro and in vivo, and demonstrate synergistic effects with other chemo- and radio- therapeutic treatments. In addition, several nanocarriers have been designed to load gossypol or its derivatives in order to expand the range of their applications and evaluate their combination effects with other anti-tumor agents. This review may serve as a reference for the rational application of gossypol analogs as anti-tumor agents.

TISSUE CULTURE AND THE STUDY OF ANTICANCER AGENTS

1966 ◽  
Vol 44 (2) ◽  
pp. 339-343 ◽  
Author(s):  
Susan Tolnai
Keyword(s):  
Fatty Acids ◽  
Tumor Cells ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Unsaturated Fatty Acids ◽  
Ascites Tumor ◽  
Mouse Tumors ◽  
Arachidonic Acids

In a quest for potential antitumor agents, more than 100 fatty acids and their derivatives were tested against transplantable mouse tumors with both in vivo and in vitro methods. Three compounds, 2,3-decenoic acid, linoleic acid, and linolenic acid, were found to arrest the growth of three types of ascites tumor cells, while 2-nonenoic, 10-undecenoic, oleic, and arachidonic acids were effective to a varying degree. The cytotoxic effects of these unsaturated fatty acids on monolayer cultures of Ehrlich ascites tumor cells and of normal mouse embryos were evaluated in experiments in which graded concentrations of the test materials incorporated in the culture medium were used.

scholarly journals Somatostatin Receptor Subtypes in Human Thymoma and Inhibition of Cell Proliferation by Octreotide in Vitro

2000 ◽  
Vol 85 (4) ◽  
pp. 1719-1726 ◽  
Author(s):  
Diego Ferone ◽  
Martin P. van Hagen ◽  
Dik J. Kwekkeboom ◽  
Peter M. van Koetsveld ◽  
Diana M. Mooy ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Binding Sites ◽  
Somatostatin Receptor ◽  
Scatchard Analysis ◽  
Receptor Subtypes ◽  
Stromal Compartment ◽  
Cultured Tumor Cells

Somatostatin (SS) and SS receptor (SSR) subtypes, code-named sst1–5, are heterogeneously expressed in the normal human thymus. This suggests their involvement in controlling the immune and/or neuroendocrine functions in this organ. Moreover, recently a high in vivo uptake of[ 111In-DTPA-d-Phe1]octreotide has been reported in patients bearing thymoma. The present study characterizes in vivo and in vitro, functional SS-binding sites in a human thymoma. A high uptake of[ 111In-DTPA-d-Phe1]octreotide was observed in the chest of a patient with myasthenia gravis due to a cortical thymoma. Specific binding of[ 125I-Tyr11]SS-14 was found on a membrane preparation of the surgically removed thymoma. Scatchard analysis showed high affinity binding sites (Kd, 47.5 ± 2.5 pmol/L) with low maximum binding capacity (23.5 ± 2.5 fmol/mg membrane protein). RT-PCR analysis showed the presence of sst1, sst2A, and a predominant sst3 messenger RNA (mRNA) expression in the tumor tissue. Primary cultured tumor cells expressed sst3 mRNA only. In contrast to the normal thymus, SS mRNA was not expressed. By immunohistochemistry, the tumor cells highly expressed sst3 receptors, weakly expressed sst1 receptors, and showed no immunostaining for sst2A receptors. sst2A immunoreactivity was found in the stromal compartment of the tumor, particularly on the endothelium of small intratumoral blood vessels. In primary cultured tumor cells, both SS and octreotide (10 nmol/L) significantly inhibited[ 3H]thymidine incorporation by 40.6% and 43.2%, respectively. The following conclusions were reached. 1) As this tumor displayed a high immunoreactivity for sst3 and the cultured tumor cells expressed the sst3 mRNA only, this SSR may be the subtype involved in the inhibition of epithelial tumor cell proliferation by octreotide in vitro. 2) A loss of endogenous SS production in this thymoma might be implicated in the uncontrolled cell growth. 3) In this case, the sst3 may play a role in determining the uptake of[ 111In-DTPA-d-Phe1]octreotide by in vivo SS receptor scintigraphy.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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