Biomolecules & Therapeutics最新文献_第10页

Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells. 皮质酮对β-淀粉样蛋白诱导的 SH-SY5Y 细胞死亡的影响

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.133

Bo Kyeong Do, Jung-Hee Jang, Gyu Hwan Park

{"title":"Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells.","authors":"Bo Kyeong Do, Jung-Hee Jang, Gyu Hwan Park","doi":"10.4062/biomolther.2023.133","DOIUrl":"10.4062/biomolther.2023.133","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ25-35-induced neurotoxicity and might be used to treat and/or prevent AD.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"77-83"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells. 硼替佐米有毒，但能诱导神经发生并抑制大鼠神经干细胞中 TUBB3 的降解

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 Epub Date: 2023-12-11 DOI: 10.4062/biomolther.2023.134

Seung Yeon Sohn, Thin Thin San, Junhyung Kim, Hyun-Jung Kim

{"title":"Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells.","authors":"Seung Yeon Sohn, Thin Thin San, Junhyung Kim, Hyun-Jung Kim","doi":"10.4062/biomolther.2023.134","DOIUrl":"10.4062/biomolther.2023.134","url":null,"abstract":"Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"65-76"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells. 通过调节吉西他滨耐药胰腺癌细胞中的α-Actinin-4，皮塞霉素具有抗增殖活性

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.109

Jee-Hyung Lee, Jin Ho Choi, Kyung-Min Lee, Min Woo Lee, Ja-Lok Ku, Dong-Chan Oh, Yern-Hyerk Shin, Dae Hyun Kim, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim, Sang Hyub Lee, Sang Kook Lee

{"title":"Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.","authors":"Jee-Hyung Lee, Jin Ho Choi, Kyung-Min Lee, Min Woo Lee, Ja-Lok Ku, Dong-Chan Oh, Yern-Hyerk Shin, Dae Hyun Kim, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim, Sang Hyub Lee, Sang Kook Lee","doi":"10.4062/biomolther.2023.109","DOIUrl":"10.4062/biomolther.2023.109","url":null,"abstract":"Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"123-135"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin. 甘草查尔酮 C 可抑制对奥沙利铂耐药的人类结直肠癌 HCT116 细胞的生长。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.167

Seung-On Lee, Sang Hoon Joo, Jin-Young Lee, Ah-Won Kwak, Ki-Taek Kim, Seung-Sik Cho, Goo Yoon, Yung Hyun Choi, Jin Woo Park, Jung-Hyun Shim

{"title":"Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin.","authors":"Seung-On Lee, Sang Hoon Joo, Jin-Young Lee, Ah-Won Kwak, Ki-Taek Kim, Seung-Sik Cho, Goo Yoon, Yung Hyun Choi, Jin Woo Park, Jung-Hyun Shim","doi":"10.4062/biomolther.2023.167","DOIUrl":"10.4062/biomolther.2023.167","url":null,"abstract":"Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"104-114"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury. (+)-Afzelechin 对微粒物质引起的肺损伤的治疗作用

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.187

Sanghee Cho, Yun Jin Park, Jong-Sup Bae

{"title":"Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury.","authors":"Sanghee Cho, Yun Jin Park, Jong-Sup Bae","doi":"10.4062/biomolther.2023.187","DOIUrl":"10.4062/biomolther.2023.187","url":null,"abstract":"Particulate matter (PM) constitutes a hazardous blend of organic and inorganic particles that poses health risks. Inhalation of fine airborne PM with a diameter of ≤ 2.5 μm (PM2.5) can lead to significant lung impairments. (+)-afzelechin (AZC), a natural compound sourced from Bergenia ligulata, boasts a range of attributes, including antioxidant, antimicrobial, anticancer, and cardiovascular effects. However, knowledge about the therapeutic potential of AZC for patients with PM2.5-induced lung injuries remains limited. Thus, in this study, we investigated the protective attributes of AZC against lung damage caused by PM2.5 exposure. AZC was administered to the mice 30 min after intratracheal instillation of PM2.5. Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were evaluated in mice exposed to PM2.5. Data demonstrated that AZC mitigated lung damage, reduced W/D weight ratio, and curbed hyperpermeability induced by PM2.5 exposure. Furthermore, AZC effectively lowered plasma levels of inflammatory cytokines produced by PM2.5 exposure. It reduced the total protein concentration in BALF and successfully alleviated PM2.5-induced lymphocytosis. Additionally, AZC substantially diminished the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1. In contrast, it elevated the protein phosphorylation of the mammalian target of rapamycin (mTOR). Consequently, the anti-inflammatory attribute of AZC positions it as a promising therapeutic agent for mitigating PM2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"162-169"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biased Dopamine D₂ Receptors Exhibit Distinct Intracellular Trafficking Properties and ERK Activation in Different Subcellular Domains. 有偏向的多巴胺 D2 受体在不同的亚细胞区表现出不同的胞内贩运特性和 ERK 激活。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 Epub Date: 2023-07-19 DOI: 10.4062/biomolther.2023.033

Shujie Wang, Lulu Peng, Kyeong-Man Kim

{"title":"Biased Dopamine D2 Receptors Exhibit Distinct Intracellular Trafficking Properties and ERK Activation in Different Subcellular Domains.","authors":"Shujie Wang, Lulu Peng, Kyeong-Man Kim","doi":"10.4062/biomolther.2023.033","DOIUrl":"10.4062/biomolther.2023.033","url":null,"abstract":"Biased signaling or functional selectivity refers to the ability of an agonist or receptor to selectively activate a subset of transducers such as G protein and arrestin in the case of G protein-coupled receptors (GPCRs). Although signaling through arrestin has been reported from various GPCRs, only a few studies have examined side-by-side how it differs from signaling via G protein. In this study, two signaling pathways were compared using dopamine D2 receptor (D2R) mutants engineered via the evolutionary tracer method to selectively transduce signals through G protein or arrestin (D2G and D2Arr, respectively). D2G mediated the inhibition of cAMP production and ERK activation in the cytoplasm. D2Arr, in contrast, mediated receptor endocytosis accompanied by arrestin ubiquitination and ERK activation in the nucleus as well as in the cytoplasm. D2Arr-mediated ERK activation occurred in a manner dependent on arrestin3 but not arrestin2, accompanied by the nuclear translocation of arrestin3 via importin1. D2R-mediated ERK activation, which occurred in both the cytosol and nucleus, was limited to the cytosol when cellular arrestin3 was depleted. This finding supports the results obtained with D2Arr and D2G. Taken together, these observations indicate that biased signal transduction pathways activate distinct downstream mechanisms and that the subcellular regions in which they occur could be different when the same effectors are involved. These findings broaden our understanding on the relation between biased receptors and the corresponding downstream signaling, which is critical for elucidating the functional roles of biased pathways.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"56-64"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10190071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-Inflammatory Herbal Extracts and Their Drug Discovery Perspective in Atopic Dermatitis. 抗炎草药提取物及其在特应性皮炎中的药物发现前景。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.102

Jae-Won Lee, Eun-Nam Kim, Gil-Saeng Jeong

引用次数: 0

Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells. 多柔比星通过刺激 p53 减轻 HepG2 细胞中游离脂肪酸诱导的脂质积累

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.200

Chawon Yun, Sou Hyun Kim, Doyoung Kwon, Mi Ran Byun, Ki Wung Chung, Jaewon Lee, Young-Suk Jung

{"title":"Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells.","authors":"Chawon Yun, Sou Hyun Kim, Doyoung Kwon, Mi Ran Byun, Ki Wung Chung, Jaewon Lee, Young-Suk Jung","doi":"10.4062/biomolther.2023.200","DOIUrl":"10.4062/biomolther.2023.200","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 μg/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"94-103"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis. 褪黑激素和Zileuton通过AKT/mTOR/NRF2信号抑制肾损伤和纤维化中的脱铁作用而发挥协同肾脏保护作用。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2023-11-01 Epub Date: 2023-05-15 DOI: 10.4062/biomolther.2023.062

Kyung Hee Jung, Sang Eun Kim, Han Gyeol Go, Yun Ji Lee, Min Seok Park, Soyeon Ko, Beom Seok Han, Young-Chan Yoon, Ye Jin Cho, Pureunchowon Lee, Sang-Ho Lee, Kipyo Kim, Soon-Sun Hong

{"title":"Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis.","authors":"Kyung Hee Jung, Sang Eun Kim, Han Gyeol Go, Yun Ji Lee, Min Seok Park, Soyeon Ko, Beom Seok Han, Young-Chan Yoon, Ye Jin Cho, Pureunchowon Lee, Sang-Ho Lee, Kipyo Kim, Soon-Sun Hong","doi":"10.4062/biomolther.2023.062","DOIUrl":"10.4062/biomolther.2023.062","url":null,"abstract":"According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"599-610"},"PeriodicalIF":3.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Stimulatory Anticancer Effect of Resveratrol Mediated by G Protein-Coupled Estrogen Receptor in Colorectal Cancer. 白藜芦醇在G蛋白偶联雌激素受体介导下对癌症大肠癌的刺激性抗癌作用。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2023-11-01 Epub Date: 2023-10-11 DOI: 10.4062/biomolther.2023.072

Nayun Kim, Junhye Kwon, Ui Sup Shin, Joohee Jung

{"title":"Stimulatory Anticancer Effect of Resveratrol Mediated by G Protein-Coupled Estrogen Receptor in Colorectal Cancer.","authors":"Nayun Kim, Junhye Kwon, Ui Sup Shin, Joohee Jung","doi":"10.4062/biomolther.2023.072","DOIUrl":"10.4062/biomolther.2023.072","url":null,"abstract":"Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"655-660"},"PeriodicalIF":3.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0