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Alleviatory effect of isoquercetin on benign prostatic hyperplasia via IGF-1/pi3k/akt/mtor pathway

Food Science and Human Wellness 2024年第3期13卷 1698-1710页

作者： Young-Jin Choi Meiqi Fan Nishala Erandi Wedamulla Yujiao Tang Eun-kyung kim Department of Food Science and Nutrition Dong-A UniversityBusan 49315Republic of Korea Center for Silver-targeted Biomaterials Brain Busan 21 Plus programDong-A UniversityBusan 49315Republic of Korea Department of Health Sciences the Graduate School of Dong-A UniversityBusan 49315Republic of Korea Division of Food Bioscience College of Biomedical and Health SciencesKonkuk UniversityChungju 27478Republic of Korea Department of Export Agriculture Faculty of Animal Science and Export AgricultureUva Wellassa UniversityBadulla 90000Sri Lanka School of Bio-Science and Food Engineering Changchun University of Science and TechnologyChangchun 130600China Nutritional Education Major Graduate School of EducationDong-A UniversityBusan 49315Republic of Korea Nutrinomics Lab.Co. Ltd.Busan 49315Republic of Korea

We evaluated the effect of isoquercetin(quercetin-O-3-glucoside-quercetin,IQ)as a functional component of Abeliophyllum disistichum Nakai ethanol extract(ADLE)on prostate cell proliferation and apoptosis and its effects on the IGF-1/pi3k/akt/mtor pathway in benign prostatic hyperplasia(BPH).Metabolites in ADLE were analyzed using UHPLC-qTOF-MS and *** was orally administered(1 or 10 mg/kg)to a testosterone propionate-induced BPH rat model,and its effects on the prostate weight were *** effect of IQ on androgen receptor(AR)signaling was analyzed in LNCaP *** IGF-1 and IQ affect the IGF-1/pi3k/akt/mtor pathway in BPH-1 cells was also *** metabolites in ADLE were identified and quantified,which confirmed that ADLE contained abundant IQ(20.88 mg/g).IQ significantly reduced the prostate size in a concentration-dependent manner in a BPH rat model,and significantly decreased the expression of AR signaling factors in the rat prostate tissue and LNCaP cells in a concentration-dependent *** also inhibited the pi3k/akt/mtor pathway activated by IGF-1 treatment in BPH-1 *** BPH-1 cells,IQ led to G0/G1 arrest and suppressed the expression of proliferation factors while inducing ***,IQ shows potential for use as a pharmaceutical and nutraceutical for BPH.

关键词： Isoquercetin Benign prostatic hyperplasia Androgen receptor signaling pi3k/akt/mtor pathway

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pi3k/akt/mtor pathway,hypoxia,and glucose metabolism:Potential targets to overcome radioresistance in small cell lung cancer

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Cancer Pathogenesis and Therapy 2023年第1期1卷 56-66页

作者： Huan Deng Yamei Chen Peijing Li Qingqing Hang Peng Zhang Ying Jin Ming Chen Department of Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiang 310022China Department of Radiation Oncology Zhejiang Key Laboratory of Radiation OncologyHangzhouZhejiang 310022China Department of Radiation Oncology Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China College of Life Sciences University of the Chinese Academy of SciencesBeijing 100049China Department of Radiation Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen UniversityGuangzhouGuangdong 510060China

Small cell lung cancer(SCLC)is a highly aggressive tumor type for which limited therapeutic progress has been ***-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment,but most patients with SCLC acquire therapeutic *** the need for more effective therapies,better elucidation of the molecular pathogenesis of SCLC is *** phosphoinositide 3-kinase(pi3k)/protein kinase B(akt)/mammalian target of rapamycin(mtor)pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid *** pathway is an important regulator of cancer cell glucose metabolism,and its activation probably effects radioresistance by influencing bioenergetic processes in *** metabolism has three main branches-aerobic glycolysis,oxidative phosphorylation,and the pentose phosphate pathway-involved in *** interaction between the pi3k/akt/mtor pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1(HIF-1)*** pi3k/akt/mtor pathway also influences glucose metabolism through other mechanisms to participate in radioresistance,including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate *** review summarizes our understanding of links among the pi3k/akt/mtor pathway,hypoxia,and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating disease.

关键词： Small cell lung cancer pi3k/akt/mtor pathway Glucose metabolism Radioresistance

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Echinoside A from Pearsonothuria graeffei Exert the Cytotoxicity to MDA-MB-231 Cells via Mitochondrial Membrane and Modulation of pi3k/akt/mtor pathway

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Journal of Ocean University of China 2023年第1期22卷 205-212页

作者： LI Hongyan CUI Huanhuan CONG Peixu XU Jie XIE Wancui WANG Yuming XUE Changhu College of Marine Science and Biological Engineering Qingdao University of Science and TechnologyQingdao 266042China College of Food Science and Engineering Ocean University of ChinaQingdao 266003China

A kind of triterpene glycosides echinoside A(EA)was extracted from sea cucumber Pearsonothuria graeffei,and its yield was about 0.78%.The purity of EA was 99.0%,and its molecular weight was 1206 *** was a linear tetrasaccharide attached to a pentacyclic triterpene *** inhibited the growth of MDA-MB-231 cells in *** antitumor effect was related to elevate ROS level,decrease mitochondrial membrane potential,enhance caspase-3 expression,induce cells apoptosis and arrest cell cycle at G2/M *** also dose-dependently suppressed the expressions of phophorylation proteins p-pi3k,p-akt,and p-mtor as analyzed by western *** results suggested that EA caused MDA-MB-231 cells apoptosis via intrinsic mitochondrial and pi3k/akt/mtor *** can be a potential anti-breast cancer agent to enhance the clinical efficacy.

关键词： Pearsonothuria graeffei echinoside A cytotoxicity pi3k/akt/mtor pathway

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Targeting the pi3k/akt/mtor pathway in epithelial ovarian cancer,therapeutic treatment options for platinum-resistant ovarian cancer

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Cancer Drug Resistance 2021年第3期4卷 573-595页

作者： Natasha Rinne Elizabeth LChristie Anastasia Ardasheva Chun Hei kwok Nikita Demchenko Caroline Low Catherine Tralau-Stewart Christina Fotopoulou Paula Cunnea Department of Surgery&Cancer Imperial College LondonHammersmith campusLondon W120NNUK Peter MacCallum Cancer Centre East MelbourneVictoria 3002Australia Department of Metabolism Digestion&Reproduction Imperial College LondonLondon W120NNUK Takeda Academic Innovation Center for External InnovationTakeda CaliforniaSan DiegoCA 92121USA

The survival rates for women with ovarian cancer have shown scant improvement in recent years,with a 5-year survival rate of less than 40%for women diagnosed with advanced ovarian ***-grade serous ovarian cancer(HGSOC)is the most lethal subtype where the majority of women develop recurrent disease and chemotherapy resistance,despite over 70%-80%of patients initially responding to platinum-based *** phosphoinositide 3-kinase(pi3k)/protein kinase B(akt)/mammalian target of rapamycin(mtor)signaling pathway regulates many vital processes such as cell growth,survival and ***,this pathway is frequently dysregulated in cancers including different subtypes of ovarian cancer,through amplification or somatic mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(pik3CA),amplification of akt isoforms,or deletion or inactivation of *** evidence indicates a role for the pi3k/akt/mtor pathway in the development of chemotherapy resistance in ovarian ***,targeting key nodes of the pi3k/akt/mtor pathway is a potential therapeutic *** this review,we outline dysregulation of pi3k signaling in ovarian cancer,with a particular emphasis on HGSOC and platinum-resistant *** review pre-clinical evidence for inhibitors of the main components of the pi3k pathway and highlight past,current and upcoming trials in ovarian cancers for different inhibitors of the *** no inhibitors of the pi3k/akt/mtor pathway have thus far advanced to the clinic for the treatment of ovarian cancer,several promising compounds which have the potential to restore platinum sensitivity and improve clinical outcomes for patients are under evaluation and in various phases of clinical trials.

关键词： Ovarian cancer high-grade serous pi3k/akt/mtor pathway chemotherapy resistance inhibitors therapeutics

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The role of the pi3k/akt/mtor pathway in brain tumor metastasis

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Journal of Cancer Metastasis and Treatment 2016年第1期2卷 80-89页

作者： Silvia Crespo Marcus kind Alexandre Arcaro Division of Pediatric Hematology/Oncology Bern University HospitalCH-3008 BernSwitzerland

The pi3k/akt/mtor(PAM)pathway is involved in a variety of cellular functions and often contributes to oncogenesis and cancer *** has been recognized that this pathway is frequently activated in the most common central nervous system cancers of adults and children,malignant gliomas and medulloblastomas(MB).In these tumors,the PAM network controls key functions necessary for cell invasion and metastasis,such as cell *** review summarizes the current knowledge about the role of PAM signaling in cell invasion and metastasis in gliomas and *** approaches to inhibit cell invasion and metastasis by targeting the PAM pathway will also be discussed.

关键词： pi3k/akt/mtor pathway glioblastoma medulloblastoma metastasis

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Particulate matterexposure inducesthe autophagy of macrophages via oxidative stress-mediated pi3k/akt/mtor pathway

Particulate matterexposure inducesthe autophagy of macrophag...

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2017第七届泛环渤海生物化学与分子生物学会学术交流会

作者： Ruijun Su Zhuoyu Li Institute of Biotechnology Key Laboratory of Chemical Biology and Molecular Engineering of Nati onal Ministry of EducationShanxi University Institutes of Biomedical Sciences Shanxi University School of Life Science Shanxi University

The global air pollution has become a major threat to ***,fineparticulate matter(PM2.5)with an aerodynamic diameter less than2.5 mm mostly originates from coal combustion,vehicle exhaustand the open sources in Chinese *** and experimental investigations havedemonstrated PM2.5 exposure was closely associated with ***,the studies about potential mechanisms of PM2.5-induced immunotoxicity were very ***,the current studies were limited and need further *** is well-known that alveolar macrophages are the immunecells from lung and mainly distribute in the respiratory tract andalveolar surface,which exert the defense function by againstforeign *** inside of thelungs mainly rely on alveolar macrophages to engulf foreign particles,which then can be removed by *** a result,the decrease ofinacrophages causes the damage of immune system that furtherresults in body’s immunity ***,there are the significance concerns between macrophages and health of human *** study mainly focuses on theeffect of PM2.5 exposure on cell autophagy of macrophages andclassifies relevant *** is the cellular process that disposes damaged orunwanted proteins and organelles via the self-digestion to generateintracellular nutrients and maintain the intracellular homeostasisduring various cell *** substrates areenfolded into massive cytoplasmic by double-membraned,with theextension and fusion of membrane edge,which results in the formation of the *** fuses with lysosomes to form autolysosomes todegrade the substrates by lysosomal hydrolases,the degradationproducts are recycled back into cytosol and reused to enhance cellsurvivalduring nutrient *** this paper,we have identified that PM2.5 exposure can make the number of macrophages,neutrophils and lymphocytes ***,decreased phagocytosis of macrophage

关键词： PM2.5 Pulmonary macrophage Autophagy Oxidative stress pi3k/akt/mtor pathway

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Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting pi3k/akt/mtor and EMT pathways

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Chinese Herbal Medicines 2024年第1期16卷 94-105页

作者： Yuanyuan Chen Shanshan Chen kaiting Chen Lanfang Ji Shuna Cui Jiangsu key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases Medical College of Yangzhou UniversityYangzhou 225009China Department of Gynecology and Obstetrics Affiliated Hospital of Yangzhou UniversityYangzhou 225009China

Objective: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil(5-FU) and magnolol against cervical ***: Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCk-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico ***: Phosphatidylinositol 3 kinase(pi3k)/protein kinase B(akt)/mammalian target of rapamycin(mtor) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of a-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of akt and pi3k and the expression of mtor were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with ***: Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the pi3k/akt/mtor and epithelial-mesenchymal transition(EMT) signaling pathways.

关键词： cervical cancer 5-fluorouracil EMT pathway magnolol network pharmacology pi3k/akt/mtor pathway

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pi3k/akt/mtor signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer

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Journal of Genetics and Genomics 2021年第7期48卷 640-651页

作者： Xuefeng Li Cheng Li Chenchen Guo Qiqi Zhao Jiayu Cao Hsin-Yi Huang Meiting Yue Yun Xue Yujuan Jin Liang Hu Hongbin Ji State key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China Department of Medical Oncology The First Affiliated HospitaHengyang MedicalSchoolUniversity of South ChinaHengyangHunan 421001China School of Life Science and Technology Shanghai Tech UniversityShanghai 200120China CAS key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to ***,the relation between the growth phenotypes and chemo-resistance of SCLC remains largely *** comprehensive bioinformatic analyses,we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to *** or semiadherent SCLC cells were enriched with activation of the pi3k/akt/mtor pathway and were highly ***,activation of the pi3k/akt/mtor pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with *** chemo-resistance could be largely overcome by combining chemotherapy with pi3k/akt/mtor pathway *** findings support that the pi3k/akt/mtor pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.

关键词： SCLC Heterogeneity Growth pattern Phenotype transition Drug resistance pi3k/akt/mtor pathway

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pi3k/akt/mtor Signaling as Targets for Developing Anticancer Agents from Marine Organisms

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Journal of Ocean University of China 2021年第3期20卷 688-694页

作者： GUO Mingyue ZUO Ling QIAO Gan LIU Minghua CAO Shousong LIN Xiukun Department of Pharmacology School of PharmacySouthwest Medical UniversityLuzhou 646000China Central Nervous System Drug key Laboratory of Sichuan Province Luzhou 646000China

The pi3k/akt/mtor signaling pathway is one of the most frequently dysregulated pathways in *** the pi3k-mediated pathway has been an important strategy for developing novel anticancer *** the past decades,more than 40 inhibitors of the pi3k/akt/mtor pathway have been developed at different clinical ***,everolimus,idelalisib,and copanlisib have been approved for clinical use by the Food and Drug Administration of the United States(FDA).However,the toxic-ity and drug resistance limit their efficiency in the *** compounds with greater potency and selectivity,as well as im-proved therapeutic indices with reduced toxicity,are clearly *** the past three decades,a lot of bioactive ingredients with anticancer effects by affecting the pi3k-mediated pathways have been found from marine *** the present mini-review,anticancer compounds from marine source that target the pi3k/akt/mtor signaling were *** molecular entities and their modes of action were *** marine compounds targeting special factors of the pi3k/akt/mtor were highlighted.

关键词： marine organisms pi3k/akt/mtor pathway anticancer activity

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Zebrafish ppp1r21 mutant as a model for the study of primary biliary cholangitis

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Journal of Genetics and Genomics 2023年第12期50卷 1004-1013页

作者： Chaoying Wu Wenfeng Zhang Yiyu Luo Chaoqing Cheng Xinjuan Wang Yan Jiang Shuang Li Lingfei Luo Yun Yang Institute of Developmental Biology and Regenerative Medicine Southwest UniversityBeibeiChongqing 400715China

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease that progresses to fibrosis and cirrhosis, resulting from the gradual destruction of intrahepatic bile ducts. Exploring genetic variants associated with PBC is essential to understand the pathogenesis of PBC. Here we identify a zebrafish balloon dog (blg) mutant with intrahepatic bile duct branching defects, exhibiting several key pathological PBC-like features, including immunodominant autoantigen PDC-E2 production, cholangiocyte apoptosis, immune cell infiltration, inflammatory activation, and liver fibrosis. blg encodes the protein phosphatase 1 regulatory subunit 21 (Ppp1r21), which is enriched in the liver and its peripheral tissues and plays a vital role in the early intrahepatic bile duct formation stage. Further studies show an excessive activation of the pi3k/akt/mtor pathway in the hepatic tissues in the mutant, while treatment with the pathway inhibitor LY294002 and rapamycin partially rescues intrahepatic bile duct branching defects and alleviates the PBC-like symptoms. These findings implicate the potential role of the Ppp1r21-mediated pi3k/akt/mtor pathway in the pathophysiology of PBC.

关键词： Zebrafish mutant ppp1r21 Primary biliary cholangitis PDC-E2 pi3k/akt/mtor pathway

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