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Antrodia cinnamomea exerts an anti-hepatoma effect by targeting PI3K/AKT-mediated cell cycle progression in vitro and in vivo

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Acta Pharmaceutica Sinica B 2022年第2期12卷 890-906页

作者： Yan Zhang Pin Lv Junmei Ma Ning Chen Huishan Guo Yan Chen Xiaoruo Gan Rong Wang Xuqiang Liu Sufang Fan Bin Cong Wenyi Kang Hebei Key Laboratory of Forensic Medicine College of Forensic MedicineHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety Key Laboratory Hebei Food Inspection and Research InstituteShijiazhuang 050091China Cardiovascular Medical Science Center Department of Cell BiologyHebei Medical UniversityShijiazhuang 050017China National R&D Center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology Chinese Academy of Medical SciencesBeijing 100730China

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver ***,its comprehensive chemical fingerprint is uncertain,and the mechanisms,especially the potential therapeutic target for anti-hepatocellular carcinoma(HCC)are still *** UPLC-Q-TOF/MS,139 chemical components were identified in *** dropping pills(ACDPs).Based on these chemical components,network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer,which were closely related with cell proliferation ***,HCC data was downloaded from Gene Expression Omnibus database(GEO).The Cancer Genome Atlas(TCGA)and Dis Ge NET were analyzed by bioinformatics,and 79 biomarkers were ***,nine targets of ACDP active components were revealed,and they were significantly enriched in PI3 K/AKT and cell cycle signaling *** affinity between these targets and their corresponding active ingredients was predicted by molecular ***,in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3 K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins,contributing to the decreased growth of liver ***,PI3 K/AKT-cell cycle appears as the significant central node in anti-liver cancer of ***.

关键词： Antrodia cinnamomea UPLC-Q-TOF/MS Anti-hepatocellular carcinoma Network pharmacology PI3K/AKT cell cycle

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Regulation of sister chromatid cohesion during the mitotic cell cycle

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Science China(Life Sciences) 2015年第11期58卷 1089-1098页

作者： ZHENG Ge YU HongTao Howard Hughes Medical Institute Department of Pharmacology University of Texas Southwestern Medical Center

Orderly execution of two critical events during the cell cycle––DNA replication and chromosome segregation––ensures the stable transmission of genetic materials. The cohesin complex physically connects sister chromatids during DNA replication in a process termed sister chromatid cohesion. Timely establishment and dissolution of sister chromatid cohesion is a prerequisite for accurate chromosome segregation, and is tight regulated by the cell cycle machinery and cohesin-associated proteins. In this review, we discuss recent progress in the molecular understanding of sister chromatid cohesion during the mitotic cell cycle.

关键词： cell cycle mitosis sister chromatid cohesion cohesin cohesin loading cohesin release DNA replication cohesion estab-lishment

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Overexpression of p27^(KIP1)induced cell cycle arrest in G_1 phase and subsequent apoptosis in HCC-9204 cell line

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World Journal of Gastroenterology 2000年第4期6卷 513-521页

作者： Jiang Li Xin Ke Yang Xin Xin Yu Meng Liang Ge Wen Liang Wang Jie Zhang Yun De Hou Department of Pathology,Fourth Military Medical University,Xi’an 710033,Shaanxi Province,China State Key Laboratory for Molecular Virology and Genetic Engineering,Beijing 100052,China Department of Dermatology,Beijing Hospital,Beijing 100016,China Institute of Radiation Medicine,Beijing 100085,China 第四军医大学陕西西安中国预防医学科学院病毒所北京中国预防医学科学院病毒所分子病毒基因工程国家重点实验室北京北京医院北京解放军军事医学科学院放射医学所北京

AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-9204 cells. This study is to investigate whether p27KIP1 plays an important role in this process. MEHODS In order to elucidate the exact function of p27KIP1 in this process, a zinc inducible p27KIP1 stable transfectant and transient p27KIP1- GFP fusion transfectant were constructed. The effects of inducible p27KIP1 on cell growth, cell cycle arrest and apoptosis were examined in the mock, control pMD vector, and pMD-KIP1 transfected HCC-9204 cells. RESULTS This p27KIP1-GFP transfectant may transiently express the fusion gene. The cell growth was reduced by 35% at 48 h of p27KIP1 induction with zinc treatment as determined by trypan blue exclusion assay. These differences remained the same after 72 h of p27KIP1 expression, p27KIP1 caused cell cycle arrest after 24 h of induction, with 40% increase in G1 population. Prolonged p27KIP1 expression in this cell line induced apoptotic cell death reflected by TUNEL assay. Fourty-eight h and 72 h of p27KIP1 expression showed a characteristic DNA ladder on agarose gel electrophoresis.

关键词： p27^(KIP1) apoptosis cell cycle inducible expression system carcinoma hepatocellular liver neoplasms

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In Silico Identification of Co-transcribed Core cell cycle Regulators and Transcription Factors in Arabidopsis

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Journal of Integrative Plant Biology 2007年第8期49卷 1253-1260页

作者： Yixing Wang Ming Yang Department of Botany Oklahoma State University Stillwater OK 74078 USA

Regulatory networks involving transcription factors and core cell cycle regulators are expected to play crucial roles in plant growth and development. In this report, we describe the identification of two groups of co-transcribed core cell cycle regulators and transcription factors via a two-step in silico screening. The core cell cycle regulators include TARDY ASYNCHRONOUS MEIOSIS （CYCA1;2）, CYCB1;1, CYCB2;1, CDKB1;2, and CDKB2;2 while the transcription factors include CURLY LEAF, AINTEGUMENTA, a MYB protein, two Forkhead-associated domain proteins, and a SCARECROW family protein. Promoter analysis revealed a potential web of cross- and self-regulations among the identified proteins. Because one criterion for screening for these genes is that they are predominantly transcribed in young organs but not in mature organs, these genes are likely to be particularly involved in Arabidopsis organ growth.

关键词： Arabidopsis cell cycle cyclin-dependent kinases cyclins transcription factors.

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CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 442-454页

作者： Wen CAO Shunnan YAO Anqi LI Haoguang CHEN Enfan ZHANG Liqin CAO Jinna ZHANG Yifan HOU Zhenfeng DAI Jing CHEN Xi HUANG Li YANG Zhen CAI Bone Marrow Transplantation Center the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China Institute of Hematology Zhejiang UniversityHangzhou 310058China School of Medicine Zhejiang UniversityHangzhou 310058China

CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancers,such as acute promyelocytic leukemia and non-Hodgkin's ***,no studies have yet investigated whether CUDC-101 is effective against ***,we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma(MM)cell lines and induces cell apoptosis in a time-and dose-dependent ***,CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase(PI3K)and HDAC,and regulated the cell cycle G2/M ***,we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma *** is one of the important drugs in MM treatment,and we investigated whether CUDC-101 has a synergistic or additive effect with *** results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase ***,our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib,which provides insights into exploring new strategies for MM treatment.

关键词： CUDC-101 Multiple myeloma Bortezomib Epidermal growth factor receptor(EGFR) cell cycle

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Expression dynamics of periodic transcripts during cancer cell cycle progression and their correlation with anticancer drug sensitivity

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Military Medical Research 2023年第4期10卷 444-460页

作者： Chun‑Xiao Li Jin‑Song Wang Wen‑Na Wang Dong‑Kui Xu Yan‑Tong Zhou Fang‑Zhou Sun Yi‑Qun Li Feng‑Zhu Guo Jia‑Lu Ma Xue‑Yan Zhang Meng‑Jiao Chang Bing‑He Xu Fei Ma Hai‑Li Qian State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of VIP National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms,among which transcriptional regulation is one of the most important *** splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell ***,the patterns of transcript isoform expression in the cell cycle are *** targeting cell cycle checkpoints are commonly used as anticancer therapies,but none of them have been designed or evaluated at the alternative splicing transcript *** utility of these transcripts as markers of cell cycle-related drug sensitivity is still unknown,and studies on the expression patterns of cell cycle-targeting drug-related transcripts are also ***:To explore alternative splicing patterns during cell cycle progression,we performed sequential transcriptomic assays following cell cycle synchronization in colon cancer HCT116 and breast cancer MDA-MB-231 cell lines,using flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples,and we developed a new algorithm to describe the periodic patterns of transcripts fluctuating during the cell *** of Drug Sensitivity in Cancer(GDSC)drug sensitivity datasets and Cancer cell Line Encyclopedia(CCLE)transcript datasets were used to assess the correlation of genes and their transcript isoforms with drug *** identified transcripts associated with typical drugs targeting cell cycle by determining correlation *** assays were used to confirm the effect of ENST00000257904 against cyclin dependent kinase 4/6(CDK4/6)***,alternative splicing transcripts associated with mitotic(M)phase arrest were analyzed using an RNA synthesis inhibition assay and transcriptome ***:We established high-resolution transcriptome datasets of synchronized cell cycle samples from colon cancer HCT11

关键词： cell cycle Alternative splicing Transcriptome Drug resistance Cyclin dependent kinase 4/6 inhibitor,Dolichyl-phosphate mannosyltransferase polypeptide 2

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Effect of constant compressive stress induced by imitating tuina stimulation with various durations on the cell cycle,cellular secretion,apoptosis,and expression of myogenic differentiation and myogenic factor 5 of rat skeletal muscle cells in vitro

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Journal of Traditional Chinese Medicine 2020年第4期40卷 550-561页

作者： Lu Qunwen Su Chengguo Liu Huahui Luo Caigui Yan Bohua College of Acupuncture and Tuina Chengdu University of Traditional Chinese MedicineChengdu 610075China Department of Massage Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China National Clinical Trial Center of Chinese Med icine(Chengdu GCP Center) Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

OBJECTIVE:To investigate the effect of constant compressive stress induced by imitating Tuina stimulation with various durations on the cell cycle,cellular secretion,apoptosis,and expression of myogenic regulatory factors(MRFs),myogenic factor 5(Myf5)and myogenic differentiation(MyoD)of rat skeletal muscle cells(RSkMCs)in ***:Third passage RSkMCs were subjected to constant compressive stresses with various durations at 2000μstrain for 15,30,60,90,and 120 min via a four-point bending *** control group(CG)was cultured in the absence of mechanical *** of the cell cycle and apoptosis rate were detected by flow cytometry(FCM).The concentrations of interleukin 6(IL-6)/prostaglandin E2(PGE2)and nitric oxide(NO)in supernatants were determined by enzyme-linked immunosorbent assays and the nitrate reductase method,*** of Myf5 and MyoD was detected by ***:Compared with the CG,a significant alteration was observed in the synthesis phase fraction(SPF)(Pcell cycle,secretion,apoptosis,and Myf5 and MyoD expression of RSkMCs were regulated by compressive stress in a time-dependent *** and PI were inhibited

关键词： Tuina Muscle,skeletal cell cycle Apoptosis Bodilysecretions Myogenic regulatory factor 5 Compressive stress

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Discovery of small molecule degraders for modulating cell cycle

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Frontiers of Medicine 2023年第5期17卷 823-854页

作者： Liguo Wang Zhouli Yang Guangchen Li Yongbo Liu Chao Ai Yu Rao MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologyTsinghua UniversityBeijing100084China Beijing Tsinghua Changgung Hospital School of Clinical MedicineTsinghua UniversityBeijing102218China

The cell cycle is a complex process that involves DNA replication,protein expression,and cell *** of the cell cycle is associated with various ***-dependent kinases(CDKs)and their corresponding cyclins are major proteins that regulate the cell *** contrast to inhibition,a new approach called proteolysis-targeting chimeras(PROTACs)and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins,achieving targeted *** field of PROTACs and molecular glues has developed rapidly in recent *** this article,we aim to summarize the latest developments of CDKs and cyclin protein *** selectivity,application,validation and the current state of each CDK degrader will be ***,possible methods are discussed for the development of degraders for CDK members that still lack ***,this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders,which will be helpful for researchers working on this topic.

关键词： PROTAC molecular glue degrader cell cycle CDK cyclin

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E2F4 regulates the cell cycle and DNA replication in the silkworm,Bombyx mori

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Insect Science 2022年第4期29卷 1006-1016页

作者： Peng Chen Ling Wang Yan-Bi Long Guang-Yan Liang Xiu Yang Zhan-Qi Dong Xia Jiang Yan Zhu Min-Hui Pan Cheng Lu State Key Laboratory of Silkworm Genome Biology Southwest UniversityChongqingChina Key Laboratory of Sericultural Biology and Genetic Breeding Ministry of Agriculture and Rural AffairsSouthwest UniversityChongqingChina

The E2F family of transcription factors is crucial for cell cycle progression and cell fate *** E2Fs have been widely studied in mammals,there have been few studies performed in ***,we determined the function of E2F4 in the silkworm,Bombyx *** demonstrate that E2F proteins are highly conserved among species from lower animals to higher *** of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S *** results indicate that BmE2F4 is important in cell cycle *** also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk ***,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the *** of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S *** findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.

关键词： Bm14-3-35 Bombyx mori cell cycle E2F transcription factors E2F4 insect

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Cdk5 and aberrant cell cycle activation at the core of neurodegeneration

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Neural Regeneration Research 2023年第6期18卷 1186-1190页

作者： Raquel Requejo-Aguilar Department of Biochemistry and Molecular Biology University of CórdobaCórdobaSpain Maimónides Biomedical Research Institute of Córdoba(IMIBIC) 14071 CórdobaSpain

Neurodegenerative diseases are caused by the progressive loss of specific *** exact mechanisms of action of these diseases are unknown,and many studies have focused on pathways related to abnormal accumulation and processing of proteins,mitochondrial dysfunction,and oxidative stress leading to apoptotic ***,a growing body of evidence indicates that aberrant cell cycle re-entry plays a major role in the pathogenesis of *** activation of the cell cycle in mature neurons could be promoted by several signaling mechanisms,including c-Jun N-terminal kinases,p38 mitogen-activated protein kinases,and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades;post-translational modifications such as Tau-phosphorylation;and DNA damage *** all these events,implicated Cdk5,a proline-directed serine/threonine protein kinase,seems to be responsible for several cellular processes in neurons including axon growth,neurotransmission,synaptic plasticity,neuronal migration,and maintenance of neuronal ***,under pathological conditions,Cdk5 dysregulation may lead to cell cycle re-entry in post-mitotic ***,Cdk5 hyperactivation,by its physiologic activator p25,hyper-phosphorylates downstream substrates related to neurodegenerative *** review summarizes factors such as oxidative stress,DNA damage response,signaling pathway disturbance,and Ubiquitin proteasome malfunction contributing to cell cycle re-entry in post-mitotic *** also describes how all these factors are linked to a greater or lesser extent with ***,it offers a global vision of the function of cell cycle-related proteins in mature neurons with a focus on Cdk5 and how this protein contributes to the development of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease by cell cycle activation.

关键词： Alzheimer´s disease amyotrophic lateral sclerosis apoptosis Cdk5 cell cycle Huntington´s disease neurodegeneration neuron oxidative stress Parkinson´s disease signaling Tau phosphorylation

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