10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2019/09/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2019/09/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates.

Cancer Med. 2019 Sep 10;:

Authors: De Bastiani MA, Klamt F

Abstract
BACKGROUND: Lung adenocarcinoma is the major cause of cancer-related deaths in the world. Given this, the importance of research on its pathophysiology and therapy remains a key health issue. To assist in this endeavor, recent oncology studies are adopting Systems Biology approaches and bioinformatics to analyze and understand omics data, bringing new insights about this disease and its treatment.
METHODS: We used reverse engineering of transcriptomic data to reconstruct nontumorous lung reference networks, focusing on transcription factors (TFs) and their inferred target genes, referred as regulatory units or regulons. Afterwards, we used 13 case-control studies to identify TFs acting as master regulators of the disease and their regulatory units. Furthermore, the inferred activation patterns of regulons were used to evaluate patient survival and search drug candidates for repositioning.
RESULTS: The regulatory units under the influence of ATOH8, DACH1, EPAS1, ETV5, FOXA2, FOXM1, HOXA4, SMAD6, and UHRF1 transcription factors were consistently associated with the pathological phenotype, suggesting that they may be master regulators of lung adenocarcinoma. We also observed that the inferred activity of FOXA2, FOXM1, and UHRF1 was significantly associated with risk of death in patients. Finally, we obtained deptropine, promazine, valproic acid, azacyclonol, methotrexate, and ChemBridge ID compound 5109870 as potential candidates to revert the molecular profile leading to decreased survival.
CONCLUSION: Using an integrated transcriptomics approach, we identified master regulator candidates involved with the development and prognostic of lung adenocarcinoma, as well as potential drugs for repurposing.

PMID: 31503425 [PubMed - as supplied by publisher]

Organogold drug Auranofin exhibits anti-melanogenic activity in B16F10 and MNT-1 melanoma cells.

Arch Dermatol Res. 2019 Sep 09;:

Authors: Goenka S, Simon SR

Abstract
Auranofin (AF) is an organogold FDA-approved drug for treating rheumatism and has been repurposed for several pharmacological applications based on its anti-bacterial, anti-fungal and anti-inflammatory activities. To the best of our knowledge, there has been no study on effects of AF on melanogenesis yet. Hence, in this work, we studied the effect of AF on melanogenesis using B16F10 mouse melanoma cells and validated results in MNT-1 human melanoma cells. Melanogenesis assay was conducted with concentrations of AF determined to be nontoxic in B16F10 cells as well as HaCaT human epidermal cell line for a duration of 48 h, followed by various assays to delineate mechanisms of melanogenesis inhibition. Ultrastructural analysis was conducted to study further if AF affected melanosome maturation and protein levels of a key melanogenic protein, tyrosinase, and the maturation signaling molecule, cyclic adenosine monophosphate (cAMP), was estimated. Our results demonstrate that AF at nontoxic concentrations of 0.25-1 µM significantly inhibited melanin synthesis in a dose-dependent manner with significant inhibition of 32.85% at 1 µM. The study of mechanisms of melanogenesis inhibition revealed that AF inhibited tyrosinase activity in lysates of B16F10 cells but did not show a direct effect on purified mushroom tyrosinase activity or on copper chelation in a cell-free system, nor did it affect levels of B16F10 tyrosinase protein levels. However, AF significantly down-regulated cAMP levels, inhibited cellular ROS and increased number of melanosomes in immature stages, and also exhibited anti-melanogenic activity in B16F10-HaCaT cocultures. Furthermore, AF showed anti-melanogenic efficacy in MNT-1 cell monocultures and cocultures with an inhibition of intracellular tyrosinase activity. In summary, our results demonstrate a proof-of-principle for AF as a depigmenting agent for hyperpigmentation disorders and adjuvant for melanoma therapeutics.

PMID: 31501921 [PubMed - as supplied by publisher]

Methylxanthines: Potential Therapeutic Agents for Glioblastoma.

Pharmaceuticals (Basel). 2019 Sep 07;12(3):

Authors: Pérez-Pérez D, Reyes-Vidal I, Chávez-Cortez EG, Sotelo J, Magaña-Maldonado R

Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Currently, treatment is ineffective and the median overall survival is 20.9 months. The poor prognosis of GBM is a consequence of several altered signaling pathways that favor the proliferation and survival of neoplastic cells. One of these pathways is the deregulation of phosphodiesterases (PDEs). These enzymes participate in the development of GBM and may have value as therapeutic targets to treat GBM. Methylxanthines (MXTs) such as caffeine, theophylline, and theobromine are PDE inhibitors and constitute a promising therapeutic anti-cancer agent against GBM. MTXs also regulate various cell processes such as proliferation, migration, cell death, and differentiation; these processes are related to cancer progression, making MXTs potential therapeutic agents in GBM.

PMID: 31500285 [PubMed]

Binding of acarbose, an anti-diabetic drug to lysozyme: a combined structural and thermodynamic study.

J Biomol Struct Dyn. 2018 10;36(13):3354-3361

Authors: Dileep KV, Nithiyanandan K, Remya C

PMID: 28984494 [PubMed - indexed for MEDLINE]

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Teprenone in Patients with Alzheimer's Disease.

J Alzheimers Dis. 2019 Sep 03;:

Authors: Yokoyama S, Yoshinaga T, Matsuzaki J, Suzuki H

Abstract
BACKGROUND: Teprenone (geranylgeranylacetone), an anti-ulcer agent, has been reported to inhibit amyloid-β increase, senile plaque formation, and neuronal degeneration, and improve memory in mouse models of Alzheimer's disease (AD).
OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled study to ascertain teprenone's therapeutic ability for AD.
METHODS: Patients with mild to moderate AD, with a Mini-Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil +  placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale-cognitive subscale (ADAS-J cog) and other evaluations, respectively, including MMSE scores, during a 12-month period after the first administration.
RESULTS: Forty-two and thirty-seven patients were allocated to the teprenone and placebo groups, respectively. ADAS-J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, - 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively.
CONCLUSION: Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas.
TRIAL REGISTRATION: UMIN ID: UMIN000016843.

PMID: 31498121 [PubMed - as supplied by publisher]

Repurposed quinacrine synergizes with cisplatin, reducing the effective dose required for treatment of head and neck squamous cell carcinoma.

Oncotarget. 2019 Aug 27;10(50):5229-5244

Authors: Bryant J, Batis N, Franke AC, Clancey G, Hartley M, Ryan G, Brooks J, Southam AD, Barnes N, Parish J, Roberts S, Khanim F, Spruce R, Mehanna H

Abstract
Despite highly toxic treatments, head and neck squamous cell carcinoma (HNSCC) have poor outcomes. There is an unmet need for more effective, less toxic therapies. Repurposing of clinically-approved drugs, with known safety profiles, may provide a time- and cost-effective approach to address this need. We have developed the AcceleraTED platform to repurpose drugs for HNSCC treatment; using in vitro assays (cell viability, clonogenic survival, apoptosis) and in vivo models (xenograft tumors in NOD/SCID/gamma mice). Screening a library of clinically-approved drugs identified the anti-malarial agent quinacrine as a candidate, which significantly reduced viability in a concentration dependent manner in five HNSCC cell lines (IC50 0.63-1.85 μM) and in six primary HNSCC samples (IC50 ~2 μM). Decreased clonogenic survival, increased apoptosis and accumulation of LC3-II (indicating altered autophagy) were also observed. Effects were additional to those resulting from standard treatments (cisplatin +/- irradiation) alone. In vivo, daily treatment with 100 mg/kg oral quinacrine plus cisplatin significantly inhibited tumor outgrowth, extending median time to reach maximum tumor volume from 20 to 32 days (p < 0.0001) versus control, and from 28 to 32 days versus 2 mg/kg cisplatin alone. Importantly, combination therapy enabled the dose of cisplatin to be halved to 1 mg/kg, whilst maintaining the same impairment of tumor growth. Treatment was well tolerated; murine plasma levels reached a steady concentration of 0.5 μg/mL, comparable to levels achievable and tolerated in humans. Consequently, due to its favorable toxicity profile and proven safety, quinacrine may be particularly useful in reducing cisplatin dose, especially in frail and older patients; warranting a clinical trial.

PMID: 31497252 [PubMed]

Identification of Anti-staphylococcal and Anti-biofilm Compounds by Repurposing the Medicines for Malaria Venture Pathogen Box.

Front Cell Infect Microbiol. 2018;8:365

Authors: Bhandari V, Chakraborty S, Brahma U, Sharma P

Abstract
There has been an alarming increase in infections caused by antimicrobial-resistant pathogens. These infections are responsible for more than half a million deaths globally each year. Staphylococcus aureus is one of the deadliest bacterial pathogen responsible for nosocomial and community acquired infections. The open-access Pathogen Box (PBox) provides a potential platform to identify new treatment options against antibiotic-resistant bacteria by repurposing it. In this study, we have screened the PBox library comprised of ~400 compounds to identify novel anti-staphylococcal compounds. in vitro antimicrobial screening using S. aureus isolates, ATCC 29213 (methicillin-sensitive) and ATCC 700699 (methicillin-resistant) revealed 13 compounds which showed highly potent antibacterial activity against both planktonic and biofilm state. The 13 compounds were not found cytotoxic to mouse macrophage cell line, RAW264.7. Out of the 13 compounds, only MMV687251 and MMV676477 revealed structural similarity with vancomycin by comparing their atomic pair fingerprints using Tanimoto coefficient method. The structural similarities may indicate similar mode of action like vancomycin for the two compounds. Our result showed that PBox compounds offer a promising lead for the development of new anti-staphylococcal treatment options.

PMID: 30406042 [PubMed - indexed for MEDLINE]

Drug repurposing for Alzheimer's disease based on transcriptional profiling of human iPSC-derived cortical neurons.

Transl Psychiatry. 2019 Sep 06;9(1):220

Authors: Williams G, Gatt A, Clarke E, Corcoran J, Doherty P, Chambers D, Ballard C

Abstract
Alzheimer's disease is a complex disorder encompassing multiple pathological features with associated genetic and molecular culprits. However, target-based therapeutic strategies have so far proved ineffective. The aim of this study is to develop a methodology harnessing the transcriptional changes associated with Alzheimer's disease to develop a high content quantitative disease phenotype that can be used to repurpose existing drugs. Firstly, the Alzheimer's disease gene expression landscape covering severe disease stage, early pathology progression, cognitive decline and animal models of the disease has been defined and used to select a set of 153 drugs tending to oppose disease-associated changes in the context of immortalised human cancer cell lines. The selected compounds have then been assayed in the more biologically relevant setting of iPSC-derived cortical neuron cultures. It is shown that 51 of the drugs drive expression changes consistently opposite to those seen in Alzheimer's disease. It is hoped that the iPSC profiles will serve as a useful resource for drug repositioning within the context of neurodegenerative disease and potentially aid in generating novel multi-targeted therapeutic strategies.

PMID: 31492831 [PubMed - in process]

Molecular Docking: Shifting Paradigms in Drug Discovery.

Int J Mol Sci. 2019 Sep 04;20(18):

Authors: Pinzi L, Rastelli G

Abstract
Molecular docking is an established in silico structure-based method widely used in drug discovery. Docking enables the identification of novel compounds of therapeutic interest, predicting ligand-target interactions at a molecular level, or delineating structure-activity relationships (SAR), without knowing a priori the chemical structure of other target modulators. Although it was originally developed to help understanding the mechanisms of molecular recognition between small and large molecules, uses and applications of docking in drug discovery have heavily changed over the last years. In this review, we describe how molecular docking was firstly applied to assist in drug discovery tasks. Then, we illustrate newer and emergent uses and applications of docking, including prediction of adverse effects, polypharmacology, drug repurposing, and target fishing and profiling, discussing also future applications and further potential of this technique when combined with emergent techniques, such as artificial intelligence.

PMID: 31487867 [PubMed - in process]

Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial.

F1000Res. 2018;7:1797

Authors: Jakola AS, Werlenius K, Mudaisi M, Hylin S, Kinhult S, Bartek J, Salvesen Ø, Carlsen SM, Strandéus M, Lindskog M, Löfgren D, Rydenhag B, Carstam L, Gulati S, Solheim O, Bartek J, Solheim T

Abstract
Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O 6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.

PMID: 30647912 [PubMed - indexed for MEDLINE]

A new scope for orlistat: Effect of approved anti-obesity drug against experimental microsporidiosis.

Med Mycol. 2019 Feb 01;57(2):181-195

Authors: Abou-El-Naga IF, Said DE, Gaafar MR, Ahmed SM, El-Deeb SA

Abstract
As the current therapies for intestinal microsporidiosis are either inconsistent in their efficacies or hampered by several adverse effects, alternative antimicrosporidial agents are being sought. The present study is the first that was designed to evaluate the potency of orlistat, an approved anti-obesity drug, against intestinal microsporidiosis caused by both Enterocytozoon bieneusi and Encephalitozoon intestinalis. Results were assessed through studying fecal and intestinal spore load, intestinal histopathological changes, viability, and infectivity of spores from treated animals. Results showed that orlistat has promising antimicrosporidia potential, with better results in E. intestinalis than E. bieneusi. The animals that received orlistat showed statistically significant decrease in the fecal and intestinal spore load, when compared to the corresponding control infected nontreated mice. The results were insignificant compared to fumagillin and albendazole. Light microscopic examination of stained intestinal sections revealed amelioration of the pathological changes and decreased inflammatory cells detected in the control infected nontreated mice. Spores encountered from stool of orlistat-treated E. bieneusi and E. intestinalis mice showed low viability and significant reduction of infectivity versus their control. Thus, considering the results of the present work, orlistat proved its effectiveness against the intestinal microsporidial infection.

PMID: 29529254 [PubMed - indexed for MEDLINE]

In silico drug repositioning: from large-scale transcriptome data to therapeutics.

Arch Pharm Res. 2019 Sep 03;:

Authors: Kwon OS, Kim W, Cha HJ, Lee H

Abstract
Drug repositioning is an attractive alternative to conventional drug development when new beneficial effects of old drugs are clinically validated because pharmacokinetic and safety profiles are generally already available. Since ~ 30% of drugs newly approved by the US food and drug administration (FDA) are developed through drug repositioning, identifying novel usage for existing drugs is an emerging strategy for developing disease treatments. With advances in next-generation sequencing technologies, available transcriptome data related to diseases have expanded rapidly. Harnessing these resources enables a better understanding of disease mechanisms and drug mode of action (MOA), and moves toward personalized pharmacotherapy. In this review, we briefly outline publicly available large-scale transcriptome databases and tools for drug repositioning. We also highlight recent approaches leading to the discovery of novel drug targets, drug response biomarkers, drug indications, and drug MOA.

PMID: 31482491 [PubMed - as supplied by publisher]

A review of drug repositioning based chemical-induced cell line expression data.

Curr Med Chem. 2019 Sep 03;:

Authors: Wang F, Lei X, Wu FX

Abstract
Drug repositioning is an important area of biomedical research. The drug repositioning studies have shifted to computational approaches. Large-scale perturbation databases, such as the Connectivity Map and the Library of Integrated Network-Based Cellular Signatures, contain a number of chemical-induced gene expression profiles and provide great opportunities for computational biology and drug repositioning. One reason is that the profiles provided by the Connectivity Map and the Library of Integrated Network-Based Cellular Signatures databases show an overall view of biological mechanism in drugs, diseases and genes. In this article, we provide a review of the two databases and their recent applications in drug repositioning.

PMID: 31480994 [PubMed - as supplied by publisher]

Computational Drug Repurposing Algorithm Targeting TRPA1 Calcium Channel as a Potential Therapeutic Solution for Multiple Sclerosis.

Pharmaceutics. 2019 Sep 02;11(9):

Authors: Mihai DP, Nitulescu GM, Ion GND, Ciotu CI, Chirita C, Negres S

Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS) through neurodegeneration and demyelination, leading to physical/cognitive disability and neurological defects. A viable target for treating MS appears to be the Transient Receptor Potential Ankyrin 1 (TRPA1) calcium channel, whose inhibition has been shown to have beneficial effects on neuroglial cells and protect against demyelination. Using computational drug discovery and data mining methods, we performed an in silico screening study combining chemical graph mining, quantitative structure-activity relationship (QSAR) modeling, and molecular docking techniques in a global prediction model in order to identify repurposable drugs as potent TRPA1 antagonists that may serve as potential treatments for MS patients. After screening the DrugBank database with the combined generated algorithm, 903 repurposable structures were selected, with 97 displaying satisfactory inhibition probabilities and pharmacokinetics. Among the top 10 most probable inhibitors of TRPA1 with good blood brain barrier (BBB) permeability, desvenlafaxine, paliperidone, and febuxostat emerged as the most promising repurposable agents for treating MS. Molecular docking studies indicated that desvenlafaxine, paliperidone, and febuxostat are likely to induce allosteric TRPA1 channel inhibition. Future in vitro and in vivo studies are needed to confirm the biological activity of the selected hit molecules.

PMID: 31480671 [PubMed]

Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature.

Cancers (Basel). 2019 Aug 31;11(9):

Authors: Guerini AE, Triggiani L, Maddalo M, Bonù ML, Frassine F, Baiguini A, Alghisi A, Tomasini D, Borghetti P, Pasinetti N, Bresciani R, Magrini SM, Buglione M

Abstract
Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called "cancer stem cells". Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

PMID: 31480477 [PubMed]

Repurposing drugs to treat neurological diseases.

J Neurol. 2018 02;265(2):446-448

Authors: Massey TH, Robertson NP

PMID: 29322257 [PubMed - indexed for MEDLINE]

Efficacy of antiretroviral compounds against Toxoplasma gondii in vitro.

Int J Antimicrob Agents. 2019 Aug 31;:

Authors: Wang JL, Elsheikha HM, Li TT, He JJ, Bai MJ, Liang QL, Zhu XQ, Cong W

Abstract
The obligate intracellular parasite Toxoplasma gondii can infect nearly all warm-blooded animals including humans. Although infection with this parasite is generally benign, severe illness may occur in the infected individuals if their immunity becomes less competent, such as AIDS patients. In this study, we determined the inhibitory activity of 44 commonly used antiretroviral compounds against T. gondii in vitro. Fourteen of the 44 tested antiretroviral compounds showed potency against T. gondii at IC50 concentrations that ranged from 1.18 ± 2.21 µM (nelfinavir) to 18.89 ± 1.87 µM (trovirdine). Seven of the 14 potent antiretroviral compounds are HIV-1 protease inhibitors. We investigated whether co-administration of these 14 antiretroviral compounds interferes with the anti-T. gondii activity of the existing anti-T. gondii drugs, sulfadiazine or pyrimethamine. Results showed no significant interaction between any of the tested 14 antiretroviral compounds and pyrimethamine or sulfadiazine. These results warrant the investigation of whether the administration of the lead antiretroviral drugs with highly potent anti-T. gondii activity to AIDS patients may help in limiting the occurrence of toxoplasmic encephalitis.

PMID: 31479744 [PubMed - as supplied by publisher]

Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer.

Mol Cancer Ther. 2018 09;17(9):1859-1870

Authors: Yang Y, Mamouni K, Li X, Chen Y, Kavuri S, Du Y, Fu H, Kucuk O, Wu D

Abstract
Docetaxel resistance remains a major obstacle in the treatment of prostate cancer bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of prostate cancer in preclinical models. DRD2 is ubiquitously expressed in prostate cancer cell lines and significantly reduced in prostate cancer tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in prostate cancer cells, but effectively induces cell-cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1, and survivin and increases the expression of p53, p21, and p27. Intriguingly, bromocriptine markedly reduces androgen receptor levels, partially through Hsp90-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in prostate cancer cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in prostate cancer. Mol Cancer Ther; 17(9); 1859-70. ©2018 AACR.

PMID: 29907594 [PubMed - indexed for MEDLINE]