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Source: Biochemical Pharmacology

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Total 204 results found since Jan 2013.

The growth of siRNA-based therapeutics: updated clinical studies.
Abstract More than two decades after the natural gene-silencing mechanism of RNA interference was elucidated, small interfering RNA (siRNA)-based therapeutics have finally broken into the pharmaceutical market. With three agents already approved and many others in advanced stages of the drug development pipeline, siRNA drugs are on their way to becoming a standard modality of pharmacotherapy. The majority of late-stage candidates are indicated for rare or orphan diseases, whose patients have an urgent need for novel and effective therapies. Additionally, there are agents that have the potential to meet the need of...
Source: Biochemical Pharmacology - January 26, 2021 Category: Drugs & Pharmacology Authors: Zhang MM, Bahal R, Rasmussen TP, Manautou JE, Zhong XB Tags: Biochem Pharmacol Source Type: research

Prolonged cultured human hepatocytes as an in vitro experimental system for the evaluation of potency and duration of activity of RNA therapeutics: Demonstration of prolonged duration of gene silencing effects of a GalNAc-conjugated human hypoxanthine phosphoribosyl transferase (HPRT1) siRNA.
We report here the evaluation of a novel in vitro experimental model, prolonged cultured human hepatocytes (PCHC), as an experimental system to evaluate the potency and duration of effects of oligonucleotide therapeutics. A novel observation was made on the redifferentiation of PCHC upon prolonged culturing based on mRNA profiling of characteristic hepatic differentiation marker genes albumin, transferrin, and transthyretin. Consistent with the known de-differentiation of cultured human hepatocytes, decreases in marker gene expression were observed upon culturing of the hepatocytes for 2 days. A novel observation of re-dif...
Source: Biochemical Pharmacology - December 21, 2020 Category: Drugs & Pharmacology Authors: Yang Q, Humphreys SC, Lade JM, Li AP Tags: Biochem Pharmacol Source Type: research

Cytoplasmic expression of EGFR shRNA using a modified T7 autogene-based hybrid mRNA/DNA system induces long-term EGFR silencing and prolongs antitumor effects.
Abstract Unusual activation or overexpression of epidermal growth factor receptor (EGFR) has been found in various cancers, and therefore down-regulation of EGFR expression is recognized as a promising strategy for cancer treatment. For decades, RNAi has emerged as an effective solution to regulate gene overexpression, but transient effects of exogenous siRNA have limited the development of EGFR-targeting siRNA therapeutics. Recently, we developed T7 autogene-based hybrid mRNA/DNA system as a non-viral vector for shRNA production and reported the feasibility of long-term silencing for RFP expression as a concept o...
Source: Biochemical Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Authors: Seraj S, Jae Cho Y, Lee JW, Jun Ahn H Tags: Biochem Pharmacol Source Type: research

Proapoptotic PEDF functional peptides inhibit prostate tumor growth-A mechanistic study.
This study investigates the ability and mechanism by which the functional PEDF peptides PEDF34 and PEDF44 suppress tumor growth. The results showed that death receptor pathway was activated by PEDF34 through up-regulation of FasL and activation of caspase-8 in both xenograft tumor tissues and PC-3 cells. FasL knockdown by siRNA or JNK-p inhibition attenuated apoptosis induced by PEDF34. NF-κB and PPARγ are crucial transcription factors for FasL expression. PEDF34 up-regulated PPARγ but did not affect NF-κB. PEDF34-induced up-regulation of FasL was abolished by siRNA-mediated PPARγ knockdown or using PPARγ inhibitor G...
Source: Biochemical Pharmacology - September 24, 2014 Category: Drugs & Pharmacology Authors: Gong Q, Qiu S, Li S, Ma Y, Chen M, Yao Y, Che D, Feng J, Cai W, Ma J, Yang X, Gao G, Yang Z Tags: Biochem Pharmacol Source Type: research

Estrogen receptor mediates simvastatin-stimulated osteogenic effects in bone marrow mesenchymal stem cells.
In this study, we hypothesize that the estrogen receptor (ER) mediates simvastatin-induced osteogenic differentiation. ER antagonists and siRNA were used to determine the involvement of the ER in simvastatin-induced osteogenesis in mouse bone marrow mesenchymal stem cells (D1 cells). Osteogenesis was evaluated by mRNA expression, protein level/activity of osteogenic markers, and mineralization. The estrogen response element (ERE) promoter activity and the ER-simvastatin binding affinity were examined. Our results showed that the simvastatin-induced osteogenic effects were decreased by treatment with ERα antagonists and ER...
Source: Biochemical Pharmacology - September 24, 2015 Category: Drugs & Pharmacology Authors: Chuang SC, Chen CH, Fu YC, Tai IC, Li CJ, Chang LF, Ho ML, Chang JK Tags: Biochem Pharmacol Source Type: research

Ginsenoside Rg5 induces G2/M phase arrest, apoptosis and autophagy via regulating ROS-mediated MAPK pathways against human gastric cancer.
In this study, Rg5 could suppress cell proliferation by causing G2/M phase arrest. Treatment with Rg5 could induce apoptosis through the extrinsic death receptor and intrinsic mitochondrial pathways. Autophagy induction was demonstrated by the formation of autophagosomes and autophagy-related proteins. Rg5-induced cell death was drastically restored by the autophagy inhibitor 3-MA and apoptosis inhibitor Z-VAD-FMK. Moreover, the suppression of apoptosis weakened Rg5-induced autophagy, while the inhibition of autophagy attenuated Rg5-induced apoptosis. Further studies revealed that Rg5 induced ROS production and activated M...
Source: Biochemical Pharmacology - July 9, 2019 Category: Drugs & Pharmacology Authors: Liu Y, Fan D Tags: Biochem Pharmacol Source Type: research

NEK7 mediated assembly and activation of NLRP3 inflammasome downstream of potassium efflux in ventilator-induced lung injury.
In this study, we constructed an in vitro cyclic stretch (CS)-stimulated mouse lung epithelial (MLE-12) cell model that was transfected with NIMA-related kinase 7 (NEK7) small interfering RNA (siRNA) or scramble siRNA (sc siRNA) and pretreated with or without glibenclamide (glb). We also established a VILI mouse model, which was pretreated with glibenclamide or oridonin (Ori). Our goal was to investigate the regulatory effects of NEK7 on NLRP3 inflammasome activation and the anti-inflammatory effects of glibenclamide and oridonin on VILI. Mechanical stretch exaggerated the interaction between NEK7 and NLRP3, leading to ass...
Source: Biochemical Pharmacology - April 26, 2020 Category: Drugs & Pharmacology Authors: Liu H, Gu C, Liu M, Liu G, Wang Y Tags: Biochem Pharmacol Source Type: research

Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.
Abstract Metformin, an extensively used and well-tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer drug. On the other hand, paclitaxel (Taxol) is a new antineoplastic drug that has shown promise in the treatment of non-small cell lung cancer (NSCLC). High expression levels of excision repair cross-complementary 1 (ERCC1) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum-containing chemotherapy. In this current study, paclitaxel was found to increase phosphorylati...
Source: Biochemical Pharmacology - December 7, 2012 Category: Drugs & Pharmacology Authors: Tseng SC, Huang YC, Chen HJ, Chiu HC, Huang YJ, Wo TY, Weng SH, Lin YW Tags: Biochem Pharmacol Source Type: research

Saxifragifolin D induces the interplay between apoptosis and autophagy in breast cancer cells through ROS-dependent endoplasmic reticulum stress.
In conclusion, SD inhibits breast cancer cell growth and induces interplay between apoptosis and autophagy through ROS-mediated endoplasmic reticulum stress. It will provide molecular bases for developing SD into a drug candidate for the treatment of breast cancer. PMID: 23348250 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - January 21, 2013 Category: Drugs & Pharmacology Authors: Shi JM, Bai LL, Zhang DM, Yiu A, Yin ZQ, Han WL, Liu JS, Li Y, Fu DY, Ye WC Tags: Biochem Pharmacol Source Type: research

Modulation of A-type K(+) channels by the short-chain cobrotoxin through the protein kinase C-delta isoform decreases membrane excitability in dorsal root ganglion neurons.
In this study, we identified the functional role of cobrotoxin, the short-chain α-neurotoxin isolated from Naja atra venom, which acts in the regulation of the transient A-type K(+) currents (I(A)) and membrane excitability in dorsal root ganglion (DRG) neurons via the activation of the muscarinic M3 receptor (M3R). Our results showed that cobrotoxin increased I(A) in a concentration-dependent manner, whereas the sustained delayed rectifier K(+) currents (I(DR)) were not affected. Cobrotoxin did not affect the activation of I(A) markedly, however, it shifted the inactivation curve significantly in the depolarizing directi...
Source: Biochemical Pharmacology - February 19, 2013 Category: Drugs & Pharmacology Authors: Guo Q, Jiang YJ, Jin H, Jiang XH, Gu B, Zhang YM, Wang JG, Qin ZH, Tao J Tags: Biochem Pharmacol Source Type: research

Gene Expression Profiling for Analysis Acquired Oxaliplatin Resistant Factors in Human Gastric Carcinoma TSGH-S3 Cells: the Role of IL-6 Signaling and Nrf2/AKR1C Axis Identification.
Abstract Oxaliplatin treatment is a mainstay of treatment for advanced gastrointestinal tract cancer, but the underlying mechanisms of acquired oxaliplatin resistance remain largely obscured. We previously demonstrated that increased DNA repair capacity and copper-transporting ATPase 1 (ATP7A) level contributed to oxaliplatin resistance in the human gastric carcinoma cell line TSGH-S3 (S3). In the present study, we applied gene array technology to identify additional resistance factors in S3 cells. We found that interleukin-6 (IL-6), aldo-keto reductase 1C1 (AKR1C1), and AKR1C3 are the top 3 upregulated genes in S...
Source: Biochemical Pharmacology - August 8, 2013 Category: Drugs & Pharmacology Authors: Chen CC, Chu CB, Liu KJ, Huang CY, Chang JY, Pan WY, Chen HH, Cheng YH, Lee KD, Chen MF, Kuo CC, Chen LT Tags: Biochem Pharmacol Source Type: research

Salsalate and Adiponectin Ameliorate Hepatic Steatosis by Inhibition of the Hepatokine Feutin-A.
In conclusion, salsalate and fAd improved palmitate-induced steatosis and impairment of lipid metabolism in hepatocytes via fetuin-A inhibition through the AMPK-NFκB pathway. PMID: 23948064 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - August 12, 2013 Category: Drugs & Pharmacology Authors: Jung TW, Youn BS, Choi HY, Lee SY, Hong HC, Yang SJ, Yoo HJ, Kim BH, Baik SH, Choi KM Tags: Biochem Pharmacol Source Type: research

Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells.
Abstract Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial pr...
Source: Biochemical Pharmacology - November 10, 2013 Category: Drugs & Pharmacology Authors: Yu HS, Wang SW, Chang AC, Tai HC, Yeh HI, Lin YM, Tang CH Tags: Biochem Pharmacol Source Type: research

Heat Shock Factor 1 Confers Resistance to Hsp90 Inhibitors through p62/SQSTM1 Expression and Promotion of Autophagic Flux.
We report a mechanism by which HSF1 activation diminishes the effect of Hsp90 inhibitors geldanamycin and 17-allylaminogeldanamycin (17-AAG, tanespimycin). Silencing HSF1 with siRNA or inhibiting HSF1 activity with KRIBB11 lowers the threshold for apoptosis in geldanamycin and 17-AAG-treated cancer cells. Autophagy also mitigates the actions of Hsp90 inhibitors. Blocking autophagy with 3-methyladenine (3-MA), bafilomycin A1, or beclin 1 siRNA also lower the threshold forapoptosis. Exploring a potential relationship between HSF1 and autophagy, we monitored autophagosome formation and autophagic flux in control and HSF1-sile...
Source: Biochemical Pharmacology - November 28, 2013 Category: Drugs & Pharmacology Authors: Samarasinghe B, Wales CT, Taylor FR, Jacobs AT Tags: Biochem Pharmacol Source Type: research

Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2.
Abstract Preadipocyte migration is vital for the development of adipose tissue, which plays a crucial role in lipid metabolism. ADP-ribosylation factor 6 (ARF6) small GTPase, which regulates membrane trafficking, is activated by GTP-exchange factors (GEFs) such as cytohesin 2. Cytohesin 2 and ARF6 have previously been implicated in the regulation of 3T3-L1 preadipocyte migration. We investigated here the molecular mechanism underlying the cytohesin 2 and ARF6 mediated regulation of preadipocyte migration. Preadipocyte migration and the activation of ARF6 and ERK1/2 were studied by using a number of approaches, inc...
Source: Biochemical Pharmacology - October 20, 2014 Category: Drugs & Pharmacology Authors: Davies JC, Tamaddon-Jahromi S, Jannoo R, Kanamarlapudi V Tags: Biochem Pharmacol Source Type: research