Repurposing Antipsychotics of the Diphenylbutylpiperidine Class for Cancer Therapy

Publication date: Available online 13 October 2019Source: Seminars in Cancer BiologyAuthor(s): Vikram Shaw, Suyash Srivastava, Sanjay K. SrivastavaAbstractThe recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium channel. A correlation has been found that patients treated for schizophrenia have lower incidences of certain types of cancer, such as respiratory, prostate, and bladder cancers. These compounds have also been shown to inhibit cancer proliferation in a variety of cancer cells, including melanoma, lung carcinoma, breast cancer, pancreatic cancer, glioma, and prostate cancer, among others. Antipsychotic drugs induce apoptosis and suppress metastasis in in vitro and in vivo models through mechanisms involving p53, STAT3, STAT5, protein phosphatase 2A, cholesterol homeostasis, integrins, autophagy, USP1, wnt/β-catenin signaling, and DNA repair. Additionally, pre-clinical evidence suggests that penfluridol and pimozide act synergistically with existing chemotherapeutic agents, such as dasatinib, temozolomide, and cisplatin. Some studies have also reported that ...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research

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Publication date: Available online 15 November 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Amanda D'Espessailles, Natalia Santillana, Sofía Sanhueza, Cecilia Fuentes, Mariana CifuentesAbstractExcess adipose tissue (AT) associates with inflammation and obesity-related diseases. We studied whether calcium-sensing receptor (CaSR)-mediated NLRP3 inflammasome activation in THP-1 macrophages elevates inflammation in LS14 preadipocytes, modeling deleterious AT cell crosstalk. THP-1 macrophages exposed to Cinacalcet (CaSR activator, 2 μM, 4 h) showed elevated proinflammatory marker and NLRP3 inflammaso...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
Publication date: Available online 14 November 2019Source: Diabetes &Metabolic Syndrome: Clinical Research &ReviewsAuthor(s): Mariceli Comellas, Yamile Marrero, Florence George, Lisa MatthewsAbstractAimTo assess the age and its association with glycemic control (GC) among adults with type 2-diabetes in the United States.Materials and MaterialsData were collected from the National Nutrition Examination Survey (NHANES) 2013 -2014 (n=697), cross-sectional national survey adults with Type2 diabetes. Characteristics included retinopathy diagnosis, blood pressure, albumin-creatinine ratio, hemoglobin A1c (HbA1c), BMI, ch...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
Publication date: Available online 15 November 2019Source: Pharmacological ResearchAuthor(s): Hao Jia, Haixia Peng, Zhaoyuan HouAbstractThe LIM protein Ajuba contains an unstructured proline/glycine-rich preLIM region in the N terminus and conserved tandem LIM motifs in the C terminus. Additionally, Ajuba contains both nuclear export sequences (NES) and nuclear localization sequences (NLS), which enable Ajuba shuttle between the cytoplasm and the nucleus. Thus, Ajuba can act as a versatile scaffold participating in assembly of variety of protein complexes to execute multiple cellular functions including cell adhesion, moti...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 14 November 2019Source: Pharmacological ResearchAuthor(s): Mingxue Li, Dun Wang, Jianhua He, Lixia Chen, Hua LiAbstractB-cell lymphoma-extra large (Bcl-XL) is one of the anti-apoptotic proteins of the Bcl-2 family that is localized in the mitochondria. Bcl-XL is one of the key regulators of apoptosis that can also regulate other important cellular functions. Bcl-XL is overexpressed in many cancers, and its inhibitors have shown good therapeutic effects. Bcl-XL interacts with Beclin 1, a key factor regulating autophagy.Bcl-XL is essential for the survival of neurons and plays protective ro...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 14 November 2019Source: Pharmacological ResearchAuthor(s): Lijuan Wu, Fei Li, Changying Zhao, Yao Ming, Chunmei Zheng, Yonglin Li, Shihang Lei, Chen ChenAbstractThe incidence of ischemic cardiomyopathy (ICM) is increasing yearly, which seriously endangers human health. There is rarely any remarkable progress in the treatment of ICM from the available drugs. Recent research shows that natural herbal medicine may have beneficial effects in the prevention and treatment of cardiovascular diseases. The effective extracts of the herbs may improve myocardial ischemia through various actions, suc...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Authors: Leow K, Lynch MF, Lee J PMID: 31718228 [PubMed - as supplied by publisher]
Source: International Journal of Aging and Human Development - Category: Geriatrics Tags: Int J Aging Hum Dev Source Type: research
H. E. Chiu, V. J. Wu, Y. C. Shen, K. Venkatakrishnan and C. K. Wang*
Source: Indian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research
A. Praveena*, S. Arthi and B. Sudarmathi
Source: Indian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 15 November 2019Source: Actas Dermo-Sifiliográficas (English Edition)Author(s): M.C. Martínez-González, R.A. Martínez-González, A. Guerra-TapiaAbstractCosmetic dermatology deals with the beauty and appearance of the skin–a most important element of body image. Treatments used in cosmetic dermatology (hygiene, hydration, protection, repair) aim to enhance the characteristics of the skin, its anatomy, its function, and its vitality, to produce aesthetic improvements. Communication with the patient is essential in medical consultations and we believe ...
Source: Actas Dermo-Sifiliograficas - Category: Dermatology Source Type: research
ConclusionsThis is the first sun protection accreditation program developed for Spanish schools. Studies are needed to evaluate how this program is received and how it affects students’ sun protection behaviors.ResumenIntroducciónLa exposición solar en la infancia es el principal factor de riesgo para el desarrollo de cáncer de piel en la vida adulta. Las intervenciones basadas en programas y políticas de fotoprotección escolar han demostrado ser las estrategias más eficaces y coste-efectivas para la prevención del cáncer de piel.ObjetivosElaborar un modelo de c...
Source: Actas Dermo-Sifiliograficas - Category: Dermatology Source Type: research
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