scholarly journals Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 282
Author(s):  
Hun Ho Park ◽  
Junseong Park ◽  
Hye Joung Cho ◽  
Jin-Kyoung Shim ◽  
Ju Hyung Moon ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Cell Metabolism ◽  
Dual Therapy ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chemotherapeutic Drug ◽  
Mitochondrial Complex ◽  
Dual Inhibitors ◽  
Dual Inhibition ◽  
Tumor Bioenergetics

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.

scholarly journals METB-15. REGULATION OF BIOENERGETICS THROUGH DUAL INHIBITION OF ALDEHYDE DEHYDROGENASE AND MITOCHONDRIAL COMPLEX I SUPPRESSES GLIOBLASTOMA TUMORSPHERES

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi131-vi131 ◽  
Author(s):  
Junseong Park ◽  
Jin-Kyong Shim ◽  
Joon Hee Kang ◽  
Eui Hyun Kim ◽  
Jong Hee Chang ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Dual Inhibition

scholarly journals Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres

2017 ◽  
Vol 20 (7) ◽  
pp. 954-965 ◽  
Author(s):  
Junseong Park ◽  
Jin-Kyoung Shim ◽  
Joon Hee Kang ◽  
Junjeong Choi ◽  
Jong Hee Chang ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Dual Inhibition

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

Discovery of 1,2,4-triazole-1,3-disulfonamides as dual inhibitors of mitochondrial complex II and complex III

2015 ◽  
Vol 39 (9) ◽  
pp. 7281-7292 ◽  
Author(s):  
Hua Cheng ◽  
Yan-Qing Shen ◽  
Xia-Yan Pan ◽  
Yi-Ping Hou ◽  
Qiong-You Wu ◽  
...  
Keyword(s):  
Complex Iii ◽  
Dual Function ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Dual Inhibitors

1,2,4-Triazole-1,3-disulfonamide derivatives as dual function inhibitors of mitochondrial complex II (SQR) and complex III (cyt bc1) were discovered.

scholarly journals Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 857
Author(s):  
Inyong Jung ◽  
Hyerin Kim ◽  
Seongcheol Moon ◽  
Hyuk Lee ◽  
Bonglee Kim
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Agent ◽  
Salvia Miltiorrhiza ◽  
Cerebrovascular Diseases ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Nervous System Diseases ◽  
Salvia Miltiorrhiza Bunge ◽  
Pubmed Central ◽  
Therapeutic Benefits

Salvia miltiorrhiza Bunge (S. miltiorrhiza) is a medicinal herb that has been used for the treatment for various diseases such as cardiovascular and cerebrovascular diseases in East Asia including Korea. Considering its extensive usage as a therapeutic agent for multiple diseases, there is a need to review previous research regarding its therapeutic benefits and their mechanisms. Therefore, we searched PubMed and PubMed Central for articles reporting its therapeutic effects on certain disease groups including cancers, cardiovascular, liver, and nervous system diseases. This review provides an overview of therapeutic benefits and targets of S. miltiorrhiza, including inflammation, fibrosis, oxidative stress, and apoptosis. The findings on multi-functional properties of S. miltiorrhiza discussed in this article support the efficacy of S. miltiorrhiza extract on various diseases, but also call for further research on the multiple mechanisms that mediate its therapeutic effects.

Adenovirus-mediated transfer of the neurotrophin-3 gene into skeletal muscle of pmn mice: Therapeutic effects and mechanisms of action

1998 ◽  
Vol 160 ◽  
pp. S97-S105 ◽  
Author(s):  
G Haase ◽  
B Pettmann ◽  
E Vigne ◽  
L Castelnau-Ptakhine ◽  
H Schmalbruch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Neurotrophin 3

scholarly journals Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects ofScoparia dulcis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Geethi Pamunuwa ◽  
D. Nedra Karunaratne ◽  
Viduranga Y. Waisundara
Keyword(s):  
Complementary Therapy ◽  
Antimicrobial Activities ◽  
Mechanisms Of Action ◽  
Antidiabetic Activity ◽  
Therapeutic Effects ◽  
Bioactive Constituents ◽  
Scoparia Dulcis ◽  
The Masses ◽  
Alternative And Complementary Therapy

This review discusses the antidiabetic activities ofScoparia dulcisas well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts ofS. dulcisas well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are throughα-glucosidase inhibition, curbing of PPAR-γand increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action.S. dulcishas also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded thatS. dulciscould be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through eitherin vivoor clinical means.

scholarly journals Development of Dual Inhibitors against Alzheimer’s Disease Using Fragment-Based QSAR and Molecular Docking

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Manisha Goyal ◽  
Jaspreet Kaur Dhanjal ◽  
Sukriti Goyal ◽  
Chetna Tyagi ◽  
Rabia Hamid ◽  
...  
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Drug Targets ◽  
Combinatorial Library ◽  
Interaction Analysis ◽  
Site Specific ◽  
Cleavage Enzyme ◽  
Dual Inhibitors ◽  
Dual Inhibition ◽  
Bace 1

Alzheimer’s (AD) is the leading cause of dementia among elderly people. Considering the complex heterogeneous etiology of AD, there is an urgent need to develop multitargeted drugs for its suppression.β-amyloid cleavage enzyme (BACE-1) and acetylcholinesterase (AChE), being important for AD progression, have been considered as promising drug targets. In this study, a robust and highly predictive group-based QSAR (GQSAR) model has been developed based on the descriptors calculated for the fragments of 20 1,4-dihydropyridine (DHP) derivatives. A large combinatorial library of DHP analogues was created, the activity of each compound was predicted, and the top compounds were analyzed using refined molecular docking. A detailed interaction analysis was carried out for the top two compounds (EDC and FDC) which showed significant binding affinity for BACE-1 and AChE. This study paves way for consideration of these lead molecules as prospective drugs for the effective dual inhibition of BACE-1 and AChE. The GQSAR model provides site-specific clues about the molecules where certain modifications can result in increased biological activity. This information could be of high value for design and development of multifunctional drugs for combating AD.

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