Ferah Bulut, Emine Kacar, Batuhan Bilgin, Munevver Gizem Hekim, Muhammed Mirac Keleştemur, Zafer Sahin, Ahmet Ayar, Mete Ozcan
{"title":"Crosstalk between kisspeptin and gonadotropin-inhibitory hormone in the silence of puberty: preclinical evidence from a calcium signaling study.","authors":"Ferah Bulut, Emine Kacar, Batuhan Bilgin, Munevver Gizem Hekim, Muhammed Mirac Keleştemur, Zafer Sahin, Ahmet Ayar, Mete Ozcan","doi":"10.1080/10799893.2022.2125014","DOIUrl":"https://doi.org/10.1080/10799893.2022.2125014","url":null,"abstract":"<p><p>Kisspeptin and gonadotropin-inhibitory hormone (GnIH) are among suggested neuroendocrine modulators of reproductive function. Intracellular calcium signaling is a critical component in the regulation of a variety of physiological and pathological processes including neurotransmitter release, and, therefore, can be used as signaling indicator for investigating the involvement of kisspeptin, GnIH, and gonadotropin-releasing hormone (GnRH) release. Hence, this study investigated the effects of kisspeptin and GnIH on calcium signaling using immortalized hypothalamic cells (rHypoE-8) as a model. Kisspeptin neurons were loaded with the ratiometric calcium dye (Fura-2 AM, 1 μmol) and intracellular free calcium ([Ca<sup>2+</sup>]<sub>i</sub>) responses were quantified using digital fluorescence imaging system. Kisspeptin-10 (100, 300, and 1000 nM) caused a significant increase in [Ca<sup>2+</sup>]<sub>i</sub> in rHypoE-8 cells (<i>n</i> = 58, <i>n</i> = 64, and <i>n</i> = 49, respectively, <i>p</i> < 0.001). The kisspeptin receptor antagonist, P234, inhibited the calcium responses to kisspeptin (<i>p</i> < 0.001, <i>n</i> = 32). GnIH (100 and 1000 nM), alone, did not cause any significant change in the mean basal [Ca<sup>2+</sup>]<sub>i</sub> levels in kisspeptin cells, but GnIH attenuated the kisspeptin-evoked [Ca<sup>2+</sup>]<sub>i</sub> transients (<i>n</i> = 47, <i>p</i> < 0.001). This novel findings of [Ca<sup>2+</sup>]<sub>i</sub> signaling in <i>in vitro</i> setting implicate that kisspeptin and GnIH may exert their effects on hypothalamus-pituitary-gonadal (HPG) axis by modulating kisspeptin neurons. These results also implicate that kisspeptin neurons may have an autocrine regulation.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"608-613"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10336587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methylglyoxal enhances the proliferation of vascular smooth muscle cells via Akt phosphorylation.","authors":"Mustafa Kırça","doi":"10.1080/10799893.2022.2098328","DOIUrl":"https://doi.org/10.1080/10799893.2022.2098328","url":null,"abstract":"<p><p>Methylglyoxal (MGO) is predominantly produced as a by-product of the glycolysis pathway. The glyoxalase system effectively removes it in a healthy organism. However, this process is impaired, and MGO level is elevated in people with diabetes. MGO's effects on proliferation were mostly studied in cancer cells, and the data in other cell types are limited. This study inspected the proliferative capacity of MGO in vascular smooth muscle cells (VSMCs), which have a crucial role in atherosclerosis and restenosis. The roles of ERK1/2 MAPK and Akt phosphorylations in proliferation were determined. Telmisartan, irbesartan, and NF-κB inhibitor JSH-23's roles in protecting the cells from MGO-induced proliferation were also investigated. Primary VSMCs were isolated from the rat aorta. The proliferation was spectrophotometrically measured by using a tetrazolium salt (Wst-1). The cells were cultured in standard media (SM, glucose conc. 5.5 mM) or high glucose media (HGM, glucose conc. 25 mM; an <i>in vitro</i> model of hyperglycemia). ERK1/2 MAPK and Akt phosphorylations were determined by the western blot method. MGO triggered the proliferation at 24, 48, and 72 hrs in SM and 48 and 72 hrs in HGM. Low doses of MGO such as 1-10 µM can induce proliferation. The phosphorylated ERK1/2 MAPK and Akt participated in MGO-induced proliferation. Telmisartan, irbesartan, and JSH-23 effectively alleviated the proliferation and Akt phosphorylation. MGO could proliferate VSMCs even at low doses. Moreover, hypertensive diabetic patients might benefit from a sartan family drug to protect VSMCs from MGO-induced proliferation.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"567-572"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph P Biggane, Ke Xu, Brianna L Goldenstein, Kylie L Davis, Elizabeth J Luger, Bethany A Davis, Chris W D Jurgens, Dianne M Perez, James E Porter, Van A Doze
{"title":"Pharmacological characterization of the α<sub>2A</sub>-adrenergic receptor inhibiting rat hippocampal CA3 epileptiform activity: comparison of ligand efficacy and potency.","authors":"Joseph P Biggane, Ke Xu, Brianna L Goldenstein, Kylie L Davis, Elizabeth J Luger, Bethany A Davis, Chris W D Jurgens, Dianne M Perez, James E Porter, Van A Doze","doi":"10.1080/10799893.2022.2110896","DOIUrl":"10.1080/10799893.2022.2110896","url":null,"abstract":"<p><p>The mechanism underlying the antiepileptic actions of norepinephrine (NE) is unclear with conflicting results. Our objectives are to conclusively delineate the specific adrenergic receptor (AR) involved in attenuating hippocampal CA3 epileptiform activity and assess compounds for lead drug development. We utilized the picrotoxin model of seizure generation in rat brain slices using electrophysiological recordings. Epinephrine (EPI) reduced epileptiform burst frequency in a concentration-dependent manner. To identify the specific receptor involved in this response, the equilibrium dissociation constants were determined for a panel of ligands and compared with established binding values for α<sub>1</sub>, α<sub>2</sub>, and other receptor subtypes. Correlation and slope of unity were found for the α<sub>2A</sub>-AR, but not other receptors. Effects of different chemical classes of α-AR agonists at inhibiting epileptiform activity by potency (pEC<sub>50</sub>) and relative efficacy (RE) were determined. Compared with NE (pEC<sub>50</sub>, 6.20; RE, 100%), dexmedetomidine, an imidazoline (pEC<sub>50</sub>, 8.59; RE, 67.1%), and guanabenz, a guanidine (pEC<sub>50</sub>, 7.94; RE, 37.9%), exhibited the highest potency (pEC<sub>50</sub>). In contrast, the catecholamines, EPI (pEC<sub>50</sub>, 6.95; RE, 120%) and α-methyl-NE (pEC<sub>50</sub>, 6.38; RE, 116%) were the most efficacious. These findings confirm that CA3 epileptiform activity is mediated solely by α<sub>2A</sub>-ARs without activation of other receptor systems. These findings suggest a pharmacotherapeutic target for treating epilepsy and highlight the need for selective and efficacious α<sub>2A</sub>-AR agonists that can cross the blood-brain barrier.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"580-587"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10607954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack?","authors":"Sevilay Vural, Levent Albayrak","doi":"10.1080/10799893.2022.2097264","DOIUrl":"https://doi.org/10.1080/10799893.2022.2097264","url":null,"abstract":"<p><strong>Purpose: </strong>Even if migraine is not fatal, it is a common and challenging disease with adverse effects on individuals' lives. The lack of objective diagnostic tools causes delays in diagnosis and treatment initiation. The primary aim of this study is to reveal the diagnostic value of Calcitonin Gene-Related Peptide (CGRP) and Pentraxin-3 (PTX-3) in acute migraine. To this aim, we compared the serum CGRP and PTX-3 levels of migraine patients with acute attacks to those in healthy individuals.</p><p><strong>Material and method: </strong>A total of 135 individuals (85 patients with migraine attacks with or without aura and 50 healthy controls) participated in the study. Serum CGRP and PTX-3 levels were measured with ELISA analysis. A <i>p</i> value less than 0.05 was considered significant.</p><p><strong>Results: </strong>Serum CGRP [146.70 (21.52-413.67) vs. 65.90 (3.80-256.60) pg/mL] and PTX-3 levels [12.71 (0.62-33.97) vs. 1.01 (0.06-9.48) ng/mL] were higher in patients with migraine attack than the control group (<i>p</i> < 0.01 and <i>p</i> < 0.01, respectively). ROC analysis showed that the cutoff value for serum CGRP was 121.39 pg/mL (AUC: 0.751, Sen:%61, Spe:%64) whereas the cutoff value for PTX-3 was 4,06 ng/mL (AUC:0.876, Sen:%73, Spe:%76). Serum CGRP levels were positively correlated with pain intensity. Serum CGRP and PTX-3 levels did not differ across gender groups and presence of aura in subgroup analysis.</p><p><strong>Conclusion: </strong>Patients with acute migraine attacks have higher serum CGRP and PTX-3 levels than controls. Both biomarkers show high potential for the diagnosis of a migraine attack.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"562-566"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10359779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endothelial progenitor cells promote neural stem cell proliferation in hypoxic conditions through VEGF via the PI3K/AKT pathway.","authors":"Jingti Jing, Haoming Jiang, Lin Zhang","doi":"10.1080/10799893.2021.2019275","DOIUrl":"https://doi.org/10.1080/10799893.2021.2019275","url":null,"abstract":"<p><p>Neurons and vascular cells compose neurovascular niches in the central nervous system where endothelial cells can promote neurogenesis <i>via</i> direct and indirect effects. Neurocytes and vascular cells are gravely destroyed upon spinal cord injury, which severely affects spinal motor functions. Neurogenesis originates from neural stem cells (NSCs) and endothelial cells derived from endothelial progenitor cells (EPCs) in the spinal cord. To demonstrate whether EPCs promote NSC proliferation, we cultured NSCs with EPC-conditioned medium from hypoxic conditions (CM) and EPC-unconditioned medium (UCM), i.e. endothelial cell basal medium-2, as a control. The number of S-phase cells in CM were 54.73 ± 0.67 whereas those in UCM were 26.30 ± 0.43, and the number of cells in CM was higher than that in UCM (0.32 ± 0.0019 <i>vs</i>. 0.55 ± 0.0029). We hypothesized that the cell proliferation was promoted by vascular endothelial growth factor A (VEGFA), which is secreted by EPCs in hypoxic conditions. We then used VEGF shRNA to decrease VEGFA secretion by EPCs. NSCs were cultured in conditioned medium from shRNA transfected EPCs under hypoxia (shRNA-CM) and EPC-conditioned medium under hypoxia (CM). The number of S-phase cells in the shRNA-CM was 36.86 ± 0.49 whereas that in CM was 53.61 ± 0.89, and the number of cells in the shRNA-CM was lower than that in CM (0.55 ± 0.0032 <i>vs</i>. 0.34 ± 0.0029). These data indicate that EPCs could promote NSC proliferation in hypoxic condition through VEGFA secretion.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 5","pages":"479-485"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9199229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shahin Ahmadi, Zohreh Moradi, Ashwani Kumar, Ali Almasirad
{"title":"SMILES-based QSAR and molecular docking study of xanthone derivatives as α-glucosidase inhibitors.","authors":"Shahin Ahmadi, Zohreh Moradi, Ashwani Kumar, Ali Almasirad","doi":"10.1080/10799893.2021.1957932","DOIUrl":"https://doi.org/10.1080/10799893.2021.1957932","url":null,"abstract":"<p><p>Increasing diabetic population is one of the major health concerns all over the world. Inhibition of α-glucosidase is a clinically proved and attractive strategy to manage diabetes. In this study, robust and reliable QSAR models to predict α-glucosidase inhibitory potential of xanthone derivatives are developed by the Monte Carlo technique. The chemical structures are represented by SMILES notation without any 3D-optimization. The significance of the index of ideality correlation (IIC) with applicability domain (AD) is also studied in depth. The models developed using CORAL software by considering IIC criteria are found to be statistically more significant and robust than simple balance of correlation. The QSAR models are validated by both internal and external validation methods. The promoters of increase and decrease of activity are also extracted and interpreted in detail. The interpretation of developed models explains the role of different structural attributes in predicting the pIC<sub>50</sub> of xanthone derivatives as α-glucosidase inhibitors. Based on the results of model interpretation, modifications are done on some xanthone derivatives and 15 new molecules are designed. The α-glucosidase inhibitory activity of novel molecules is further supported by docking studies.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 4","pages":"361-372"},"PeriodicalIF":2.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39304983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adrenergic receptor behaviors of mesenchymal stem cells obtained from different tissue sources and the effect of the receptor blockade on differentiation.","authors":"Erkan Maytalman, Arash Alizadeh Yegani, Ilknur Kozanoglu, Fazilet Aksu","doi":"10.1080/10799893.2021.1957931","DOIUrl":"https://doi.org/10.1080/10799893.2021.1957931","url":null,"abstract":"<p><p>In this study, it was aimed to analyze behavioral changes of adrenergic receptors (ARs) in first three passages and osteogenic/adipogenic differentiation of mesenchymal stem cells (MSCs) derived from placenta fetal membrane (FM) and bone marrow (BM). It was also aimed to evaluate effects of receptor blockade on differentiation. We obtained first three passages of MSCs from placenta and BM samples. For cell identification, the cells were analyzed by flow cytometry using CD34, CD45 and CD3, CD105 antibodies in each passage. The effects of propranolol and phenoxybenzamine at incremental doses were analyzed by MTT. In addition, cell cultures were separately maintained with the blockers or without after second passage. After each passage and differentiation, α1A, α1B, α2A, α2B, β1, β2, β3 AR-mRNA expressions analyzed by RT-qPCR technique. BMP6 and PPARG mRNA expressions only after differentiation and passage 3 were analyzed. A microscopic examination was also performed. Our results showed that AR expression behaviors were different in MSCs obtained from different tissue sources. In particular, α<sub>1A</sub>-AR and α<sub>2A</sub>-AR were expressed with considerably high coefficients in differentiation under blocker effect in BM-derived MSCs. No such coefficients were observed in any group of placental MSCs. In addition, it was found that the blockers stimulated adipogenesis in BM-derived MSCs during osteogenic differentiation. MSCs exhibit protein expressions that vary according to source of tissue and differentiation. Given that MSCs from different sources are used for repair and modulation, our study makes implications of this variable expression intriguing in the clinical practice.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 4","pages":"349-360"},"PeriodicalIF":2.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10799893.2021.1957931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39255185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Niloofar Ghasedi, Shahin Ahmadi, Sepideh Ketabi, Ali Almasirad
{"title":"DFT based QSAR study on quinolone-triazole derivatives as antibacterial agents.","authors":"Niloofar Ghasedi, Shahin Ahmadi, Sepideh Ketabi, Ali Almasirad","doi":"10.1080/10799893.2021.1988971","DOIUrl":"https://doi.org/10.1080/10799893.2021.1988971","url":null,"abstract":"<p><p>QSAR modeling was performed on 39 quinolone-triazole derivatives against gram-positive <i>Staphylococcus aureus</i> and gram-negative <i>Pseudomonas aeruginosa</i> bacteria. The molecular structures were optimized using the DFT/B3LYP method and 6-31 G basis set. Molecular descriptors were extracted using quantum mechanical calculations. The hierarchical cluster analysis was performed for a rational subset division. The initial dataset was divided into calibration and validation sets, and modeling was done by stepwise MLR method for each of the two bacteria. Internal and external validation methods confirmed the robustness and predictability of the obtained models. According to the obtained model for <i>S. aureus</i> (<i>R</i><sup>2</sup> = 0.889, <i>R</i><sup>2</sup><sub>ext</sub> = 0.938, <i>Q</i><sup>2</sup><sub>LOO</sub> = 0.853), the four descriptors- partial atomic charges for the N1 atom in triazole and C7 of the quinolone nucleus, 4-carbonyl bond length, and <sup>13</sup>C-NMR chemical shift of 3-carboxylic acid- were found to be the descriptors controlling the activity. According to the obtained model for <i>P. aeruginosa</i> (<i>R</i><sup>2</sup> = 0.957, <i>R</i><sup>2</sup><sub>ext</sub> = 0.923, <i>Q</i><sup>2</sup><sub>LOO</sub> = 0.909), the O atom's partial charge in carbonyl, LUMO-HOMO energy gap, and logP were found to be the descriptors having the highest correlation with the antibacterial activity. Finally, some new compounds with higher activities were designed and proposed.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 4","pages":"418-428"},"PeriodicalIF":2.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39554937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"microRNA-199a downregulation alleviates hyperuricemic nephropathy <i>via</i> the PPARγ/β-catenin axis.","authors":"Peng Du, Ming Chen, Changcai Deng, Chonggui Zhu","doi":"10.1080/10799893.2021.1967392","DOIUrl":"10.1080/10799893.2021.1967392","url":null,"abstract":"<p><p>Hyperuricemia always develops into hyperuricemic nephropathy (HN). The role of microRNA (miR) in HN is less studied. We aimed to discuss the role of miR-199a in HN. The expression of miR-199a and PPARγ in renal tissues of HN rats was detected. The targeting relation between miR-199a and PPARγ was verified. The contents of SCr, UA, BUN, and mALB, renal injury-relevant biomarkers were detected, and the pathological changes of renal tissue and renal interstitial fibrosis were observed by histological staining. After miR-199a and PPARγ knockdown, the contents of SCr, BUN, and mALB and renal interstitial fibrosis were estimated. Collectively, overexpression of miR-199a aggravated the renal injury in HN rats. By contrast, inhibition of miR-199a weakened renal injury, as evidenced by decreased contents of SCr, UA, BUN, and mALB, and mitigated renal interstitial fibrosis. miR-199a targeted PPARγ. Silencing of PPARγ upregulated the levels of downstream genes of β-catenin and the contents of SCr, UA, BUN, and mALB and deteriorated renal interstitial fibrosis. Moreover, the silencing of PPARγ blocked the alleviative effects of miR-199a inhibitor on the renal injury. Overall, miR-199a targets PPARγ and activates the β-catenin pathway, thus aggravating HN, which might provide a future target for the treatment of HN.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 4","pages":"373-381"},"PeriodicalIF":2.3,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39341831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Zingerone suppresses proliferation, invasion, and migration of hepatocellular carcinoma cells by the inhibition of MTDH-mediated PI3K/Akt pathway.","authors":"Jian Fang, Huifen Zhu, Pengcheng Xu, Renya Jiang","doi":"10.1080/10799893.2021.1988970","DOIUrl":"https://doi.org/10.1080/10799893.2021.1988970","url":null,"abstract":"<p><strong>Purpose: </strong>Previous studies have proved that zingerone was a therapeutic agent for many tumors. Metadherin (<i>MTDH</i>) acts as an oncogene and is involved in tumorigenesis. The purpose of this study was to explore the underlying mechanism of zingerone that regulates <i>MTDH</i> to affect hepatocellular carcinoma (HCC) progression.</p><p><strong>Methods: </strong>CCK-8 assay was performed to detect HCC cell proliferation. The invasion and migration abilities of HCC cells were evaluated using Transwell assay. The mRNA and protein levels in cells and tissues were measured using qRT-PCR and Western blot assays. Moreover, we established the HCC xenografts nude mice to evaluate the effect of zingerone on tumor growth.</p><p><strong>Results: </strong>We found that zingerone treatment significantly inhibited HCC cell malignant phenotype and tumor growth. Moreover, <i>MTDH</i> was highly expressed in HCC tissues and cell lines and was positively associated with poor overall survival of patients with HCC. Knockdown of <i>MTDH</i> notably suppressed the proliferation, invasion, and migration capacities of HCC cells. Mechanistically, inhibition of <i>MTDH</i> by zingerone impeded the malignant biological behavior of HCC cells by inactivating the PI3K/Akt pathway.</p><p><strong>Conclusion: </strong>These results suggested that zingerone served as an effective therapeutic agent in HCC via blocking the <i>MTDH</i>-mediated PI3K/Akt pathway.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 4","pages":"409-417"},"PeriodicalIF":2.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39514698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}