Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Corrigendum to “Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study” [Curr. Res. Pharmacol. Drug Discov. 3 (2022) 100116]","authors":"Fiammetta Iannuzzo , Gianpaolo Antonio Basile , Domenica Campolo , Giovanni Genovese , Gianluca Pandolfo , Loretta Giunta , Domenica Ruggeri , Antonino Di Benedetto , Antonio Bruno","doi":"10.1016/j.crphar.2025.100215","DOIUrl":"10.1016/j.crphar.2025.100215","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100215"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The suppression of the SPHK1/S1P/S1PR3 signaling pathway diminishes EGFR activation and increases the sensitivity of non-small cell lung cancer to gefitinib","authors":"Jing Zhang ,&nbsp;Zequn Wang ,&nbsp;Xihua Wei ,&nbsp;Mengyuan Han ,&nbsp;Ribai Yan ,&nbsp;Lijie Ma ,&nbsp;Yan Pan","doi":"10.1016/j.crphar.2024.100212","DOIUrl":"10.1016/j.crphar.2024.100212","url":null,"abstract":"<div><div>Non-small-cell lung cancer (NSCLC) represents a predominant histological subtype of lung cancer, characterized by high incidence and mortality rates. Despite significant advancements in therapeutic strategies and a deeper understanding of targeted therapies in recent years, tumor resistance remains an inevitable challenge, leading to poor prognostic outcomes. Several studies have indicated that sphingosine kinase 1 (SPHK1) plays a regulatory role in epidermal growth factor receptor (EGFR) signaling, and its elevated expression may be associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Furthermore, the catalytic product of SPHK1, sphingosine 1-phosphate (S1P), along with its receptor, sphingosine 1-phosphate receptor 3 (S1PR3), plays a regulatory role in the function of the EGFR. However, the specific effects of the SPHK1/S1P/S1PR3 axis on EGFR in NSCLC, as well as the combined effects of SPHK1/S1P/S1PR3 inhibitors with the EGFR-TKI gefitinib, remain to be elucidated. In the present study, we investigated the correlation between SPHK1 expression levels and the survival rates of NSCLC patients, the relationship between SPHK1 or S1PR3 and EGFR, and the impact of SPHK1 expression on the half-maximal inhibitory concentration (IC₅₀) of gefitinib in NSCLC. In A549 cells, the phosphorylation of EGFR was significantly reduced following SPHK1 knockdown. Utilizing SPHK1/S1P/S1PR3 inhibitors, namely PF543, TY52156, and FTY720, we established that the SPHK1/S1P/S1PR3 axis modulates EGFR activation in NSCLC. Furthermore, these signaling inhibitors enhanced the anti-proliferative efficacy of the EGFR-TKI gefitinib. RNA sequencing analysis revealed substantial alterations in 85 differentially expressed genes in NSCLC cells treated with the combination of FTY720 and gefitinib. These genes were predominantly associated with pathways such as axon guidance, microRNAs in cancer, and the JAK-STAT signaling pathway, among others. Overall, targeting the SPHK1/S1P/S1PR3 signaling pathway represents a promising therapeutic strategy to enhance gefitinib sensitivity in NSCLC.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100212"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCC1 and ABCC10 as predictive biomarkers of docetaxel treatment response in prostate cancer","authors":"Nandi Ngesi ,&nbsp;Beynon Abrahams ,&nbsp;Aubrey Shoko ,&nbsp;Mamello Sekhoacha","doi":"10.1016/j.crphar.2025.100216","DOIUrl":"10.1016/j.crphar.2025.100216","url":null,"abstract":"<div><div>Prostate cancer (PCa) is a leading global health burden, with a particularly high prevalence in South Africa. Despite therapeutic advancements, chemoresistance remains a major challenge, limiting the efficacy of docetaxel and contributing to treatment failure and disease progression. Multidrug resistance (MDR), primarily mediated by ATP-binding cassette (ABC) transporters such as ABCC1 and ABCC10, has been implicated in reduced chemotherapy effectiveness. This study aimed to evaluate the association between ABCC1 and ABCC10 expression levels and docetaxel treatment response in PCa patients. A retrospective case-control study was conducted using pre-treated formalin-fixed paraffin-embedded (FFPE) tissue biopsies from PCa patients. Patients were classified into good responders (cases) and poor responders (cases) based on treatment outcomes. For each patient, tumour and adjacent normal sections were excised from FFPE samples, with normal sections serving as the control group. RNA was extracted and subjected to quantitative real-time PCR (qRT-PCR) to assess ABCC1 and ABCC10 expression levels. ABCC1 and ABCC10 were significantly upregulated in tumour sections of poor responders, whereas good responders exhibited downregulated expression in tumour sections. Importantly, normal tissue sections (controls) displayed significantly lower expression levels of both transporter genes compared to tumour sections. The overexpression of ABCC1 and ABCC10 in tumour tissues, particularly in poor responders, suggests their potential role in mediating docetaxel resistance. These findings highlight ABCC1 and ABCC10 as potential predictive biomarkers for docetaxel treatment response in PCa, warranting further investigation in prospective clinical studies.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100216"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin's impact on asprosin and FBN1 expression: Potential mechanisms beyond insulin sensitivity in type 2 diabetes in rats","authors":"Ali Dashtkar ,&nbsp;Mansour Karajibani ,&nbsp;Mohsen Saravani ,&nbsp;Roya zanganeh ,&nbsp;Hamed Fanaei","doi":"10.1016/j.crphar.2024.100207","DOIUrl":"10.1016/j.crphar.2024.100207","url":null,"abstract":"<div><h3>Background</h3><div>Asprosin, a novel adipokine released under fasting conditions, may play a significant role in the pathophysiology of type 2 diabetes mellitus (T2DM). The objective of this study is to investigate the effects of metformin on serum asprosin levels and FBN1 gene expression in white adipose tissue in male rats.</div></div><div><h3>Methods</h3><div>Thirty-two male Wistar rats were randomly and equally divided into four groups (n = 8): 1. Control Group (CON): Received standard food; 2. Non-Diabetic Metformin Group (CON + MET): Received standard food and were treated with metformin (400 mg/kg/day) for four weeks; 3. Diabetic Group (DM): Induced with T2DM; and 4. Diabetic Metformin Group (DM + MET): Induced with T2DM and treated with metformin (400 mg/kg/day) for four weeks. Finally, serum asprosin levels, lipid profiles, fasting glucose, and insulin concentrations were measured. The expression level of the FBN1 gene in white adipose tissue was quantified using quantitative real-time polymerase chain reaction (qRT-PCR).</div></div><div><h3>Results</h3><div>Serum asprosin levels were significantly higher in the DM group compared to both the CON and CON + MET groups (P &lt; 0.0001). However, serum asprosin levels were significantly lower in the DM + MET group than in the DM group (P = 0.0003). Additionally, the FBN1 gene expression level in white adipose tissue was significantly higher in the DM group compared to the CON group (P = 0.0053), while FBN1 gene expression was significantly lower in the DM + MET group than in the DM group (P &lt; 0.0001). Furthermore, lipid profile, insulin resistance, and fasting blood sugar improved in the CON + MET and DM + MET groups compared to the CON and DM groups, respectively.</div></div><div><h3>Discussion</h3><div>Our findings in diabetic male rats reveal that metformin treatment significantly downregulates FBN1 gene expression and reduces serum asprosin levels, suggesting a potential mechanism for its therapeutic benefits beyond improving insulin sensitivity.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice","authors":"Medha Satti ,&nbsp;Kavita Prasad ,&nbsp;Yash Patel ,&nbsp;Demi Poulathas ,&nbsp;Lawrence Walker ,&nbsp;Esha Paghdal ,&nbsp;Samuel Gunderson ,&nbsp;Lei Yu","doi":"10.1016/j.crphar.2025.100220","DOIUrl":"10.1016/j.crphar.2025.100220","url":null,"abstract":"<div><div>U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribution after intrathecal drug delivery. We investigated the distribution patterns of U1 Adaptor upon intrathecal bolus administration in mice. It readily distributes to CNS tissues, including the lumbar and the cervical spinal cord, and the cerebellum. Over time, the U1 Adaptor also accumulates in the periphery, both in the liver and the kidneys, while plasma levels are undetectable. Our findings provide useful information for future in-depth pharmacokinetic modeling of U1 Adaptor distribution upon intrathecal administration.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100220"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory potential of quercetin: From chemistry and mechanistic insight to nanoformulations","authors":"Diwakar Aggarwal ,&nbsp;Mayank Chaudhary ,&nbsp;Sachin Kumar Mandotra ,&nbsp;Hardeep Singh Tuli ,&nbsp;Ritu Chauhan ,&nbsp;Naveen Chandra Joshi ,&nbsp;Damandeep Kaur ,&nbsp;Laurent Dufossé ,&nbsp;Abhishek Chauhan","doi":"10.1016/j.crphar.2025.100217","DOIUrl":"10.1016/j.crphar.2025.100217","url":null,"abstract":"<div><div>Flavonoids are hydroxylated polyphenols that are abundantly produced by plants as secondary metabolites. These flavonoids hold vast therapeutic potential as they possess numerous medicinal benefits encompassing anti-inflammatory, anti-oxidative, anticancer and antiviral properties. Flavonoids render anti-inflammatory effect either by activating antioxidant pathways or by inhibiting enzymatic secretions involved in inflammatory reactions. Flavonoids like quercetin targets inflammation by modulating expression of cytokines and pro-inflammatory molecules and by inhibiting pro-inflammatory enzymes. Mode of action, absorption and bioavailability of flavonoids greatly affect their biological activity. On-going research is focussing on isolation, synthesis of flavonoid analogs and effect of flavonoids on human health by manifestation of different techniques and animal models. Unravelling the anti-inflammatory potential of flavonoids can manifest better treatment options against variety of diseases and metabolic syndromes. Additionally, enhanced bioavailability of flavonoids can result in superior pharmaceutical activities.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of nebivolol-mediated effects on bFGF-induced vascular smooth muscle cell proliferation and migration","authors":"Elaina Seemann,&nbsp;Trevor Beeler,&nbsp;Mohammed Alfarra,&nbsp;Mark Cosio,&nbsp;Charles Chan,&nbsp;Peyton Grant,&nbsp;Yingzi Chang","doi":"10.1016/j.crphar.2025.100214","DOIUrl":"10.1016/j.crphar.2025.100214","url":null,"abstract":"<div><h3>Background</h3><div>Nebivolol is a β-adrenergic receptor antagonist that has intrinsic activity on β₃-adrenergic receptors (β₃-ARs). Previous studies suggest that nebivolol inhibits bFGF-induced vascular smooth muscle cell (VSMC) proliferation and migration and vascular injury-induced neointima formation through activation of β₃-ARs. However, our recently published data shown that activation of β₃-ARs produced the opposite results, suggesting that the mechanisms of nebivolol-mediated effects are not fully understood. The current project was to study the mechanisms of nebivolol’s effects on bFGF-induced VSMC proliferation and migration by comparing to the selective β₃-AR agonist, CL316,243.</div></div><div><h3>Methods</h3><div>VSMCs isolated from Sprague Dawley rat aortas were pretreated with nebivolol or CL316,243 followed by stimulation with bFGF. Cell proliferation and migration and phosphorylation of ERK and AKT were measured.</div></div><div><h3>Results</h3><div>We found that pretreatment of VSMCs with nebivolol produced biphasic effects on bFGF-induced VSMC proliferation, manifested as potentiation at lower concentrations and inhibition at the higher concentration. The effects of low concentrations of nebivolol on bFGF-induced VSMC proliferation was blocked by the selective β₃-AR antagonist, SR59230A. Nebivolol inhibited bFGF-induced cell migration at all concentrations tested. In addition, only higher concentrations of nebivolol significantly inhibited bFGF-induced AKT phosphorylation but not ERK phosphorylation whereas CL316,243 at all concentrations tested significantly enhanced bFGF-induced VSMC proliferation and migration and higher concentrations of CL316,243 not only enhanced bFGF-induced AKT phosphorylation but also ERK phosphorylation.</div></div><div><h3>Conclusion</h3><div>Our data suggest that the effect of nebivolol on bFGF-induced cell proliferation is concentration-dependent. The enhancement on bFGF-induced cell proliferation at lower concentrations appears to be mainly mediated by activation of β₃-ARs but the inhibitory effects on bFGF-mediated cell proliferation as well as migration may occur through different mechanisms. AKT signaling is only involved in high concentrations of nebivolol-mediated effects.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100214"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems","authors":"Sunitha Sampathi ,&nbsp;Nitiraj Kulkarni ,&nbsp;D.V.R.N. Bhikshapathi ,&nbsp;Jagadish V. Tawade ,&nbsp;Nainaru Tarakaramu ,&nbsp;Rzgar Farooq Rashid ,&nbsp;Aziz Kubaev","doi":"10.1016/j.crphar.2025.100213","DOIUrl":"10.1016/j.crphar.2025.100213","url":null,"abstract":"<div><h3>Background</h3><div>The current research aims to improve the oral bioavailability of ibrutinib (IBR), a class II drug with low solubility, through the formulation of nanosponges (NSPs) that incorporate IBR, utilizing Hydroxypropyl β-cyclodextrin (HPβCD) and 1,1′-carbonyldiimidazole (CDI) as cross-linking agent.</div></div><div><h3>Methods</h3><div>IBR-loaded HPβCD-NSPs were formulated by optimizing the molar proportion of HPβCD to CDI, as well as stirring rate and duration using a design-based methodology. The synthesized nanoparticles (NSPs) were examined for size, potential, and entrapment of drug. Characterization was performed by X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC), to assess compatibility. Permeability studies were conducted, followed by in vitro and in vivo assessments.</div></div><div><h3>Results</h3><div>The optimized IBR-loaded HPβCD NSPs demonstrated a mean particle size of 145.6 ± 6.8 nm, a PDI of 0.170 ± 0.036, and an EE of 71.04 ± 2.40%. Further validation through zeta sizing, microscopic and spectral analysis, release studies, and pharmacokinetic assessments confirmed the optimization. The HPβCD NSPs demonstrated 14.96 times higher AUC0-t (area under the curve) with a Cmax increase of 6.45 times compared to the free drug, indicating a substantial improvement in bioavailability.</div></div><div><h3>Conclusion</h3><div>IBR-loaded HPβCD NSPs offer a promising strategy for improved drug release and bioavailability, which could significantly benefit melanoma treatment.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100213"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world clinical utility (effectiveness) of omalizumab as add-on therapy in patient with difficult-to-treat severe allergic asthma","authors":"Rowshne Jahan,&nbsp;Ziaul Huq","doi":"10.1016/j.crphar.2025.100218","DOIUrl":"10.1016/j.crphar.2025.100218","url":null,"abstract":"<div><h3>Background</h3><div>Severe allergic asthma (SAA) requires high-dose inhaled corticosteroids and additional medications. It poses a substantial health and financial burden. Omalizumab, an antibody that targets IgE, has improved symptoms and quality of life in severe allergic asthma (SAA) patients. Its impact in Bangladeshi patients is unknown, and this study aimed to evaluate its effectiveness in improving lung function in severe allergic asthma (SAA) patients.</div></div><div><h3>Methods</h3><div>This single-centre, real-world study aimed to assess omalizumab's effectiveness in 131 Bangladeshi patients with SAA. Information regarding demographics, BMI, and IgE levels, were collected from patients &gt;12 years with poorly controlled SAA before and 3 months after omalizumab treatment. Pulmonary function tests (PFTs), including Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1 %), FEV1/FVC (%), and Fractional Exhaled Nitric Oxide (FeNO), were performed according to established guidelines. A structured questionnaire was used for data collection. Ethical measures were taken in accordance with the current Declaration of Helsinki.</div></div><div><h3>Results</h3><div>The mean age of study population was 42.7 ± 16.15 (SD) years with majority being female (67.9 %). The mean BMI and IgE level was 28 ± 5.37 kg/m² and 594.3 ± 679.9 IU/mL respectively. The mean baseline FVC, FEV₁ and FEV₁/FVC ratio was 63.5 % ± 19.2, 61.3 % ± 21.8 and 80.4 % ± 12.6 respectively. The mean post-omalizumab FVC, FEV₁ and FEV₁/FVC ratio was 72.5 % ± 25.6, 68.3 % ± 28.2 and 79.1 % ± 13.8 respectively. The FeNO reading revealed that number of patients with &lt;25 ppb reading increased post omalizumab treatment (70.2 % vs 84 %).FEV₁ expressed was significantly higher in patients post-omalizumab treatment than at the baseline (p = 0.019) and percentage of patients with FEV₁ below the predicted 50 % was higher at baseline compared to after omalizumab treatment (31.3 % vs 23.7 %). Similarly, the FVC was significantly higher post-omalizumab treatment compared to baseline (p = 0.001). The FEV₁/FVC ratio was not significantly different post omalizumab treatment (p = 0.758).</div></div><div><h3>Conclusion</h3><div>Our study finding have suggested that omalizumab as add on therapy achieved an adequate asthma control in patients with severe allergic asthma.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100218"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing into the chemopreventive properties of synthetic 1,3,6-tri-O-galloyl-α-D-glucose (α-TGG) against glioblastoma and triple-negative breast cancer-derived cell models","authors":"Carolane Veilleux ,&nbsp;Jihane Khalifa ,&nbsp;Alain Zgheib ,&nbsp;Angélique Sabaoth Konan ,&nbsp;Roger Gaudreault ,&nbsp;Borhane Annabi","doi":"10.1016/j.crphar.2025.100219","DOIUrl":"10.1016/j.crphar.2025.100219","url":null,"abstract":"<div><div>Inflammation plays a significant role in cancer progression. Chemopreventive strategies against cellular response to pro-inflammatory cues may therefore contribute to inhibit the acquisition of an invasive phenotype. 1,3,6-Tri-O-Galloyl-β-D-Glucose (β-TGG) is a type of gallotannin naturally found in plants like <em>Paeonia lactiflora</em> and <em>Terminalia chebula.</em> Unfortunately, the overall yields of β-TGG extraction require complex purification protocols from plant sources and are relatively low. Here, a new synthetic α-anomer of TGG (α-TGG) was characterized for anti-inflammatory and anticancer biological properties. <em>In vitro</em> pro-inflammatory and epithelial-to-mesenchymal transition (EMT) cues, triggered by phorbol 12-myristate 13-acetate (PMA), concanavalin A (ConA), tumor necrosis factor (TNF) α, and transforming growth factor (TGF) β, were used to screen α-TGG in two highly aggressive human cancer cell models, namely the U87 glioblastoma and the MDA-MB-231 triple-negative breast cancer (TNBC)-derived cells. α-TGG dose-dependently inhibited ConA-mediated activation of the latent matrix metalloproteinase pro-MMP-2 into its active MMP-2 form as well as the ConA- and PMA-mediated cyclooxygenase (COX)-2 expression, two biomarkers of inflammation, in U87 cells. In MDA-MB-231, α-TGG inhibited PMA- and TNFα-mediated induction of pro-MMP-9, a marker of inflammation and invasive phenotype. Finally, in both cell lines, α-TGG further inhibited TGFβ-induced chemotaxis, as well as TGFβ-induced Smad2 phosphorylation and Snail expression, crucial upstream signaling pathway and downstream biomarkers associated with EMT. Collectively, we confirm that α-TGG retained potent anti-inflammatory and anti-invasive pharmacological properties which support its chemopreventive potential.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100219"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}