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Journal of Traditional Chinese Medical Sciences 2024年第1期11卷 67-77页

作者： Amrita Pal Ribhu Ray Anirban Chouni Subhadip Hajra Santanu Paul department of Botany University of CalcuttaKolkata 700019India department of cancer chemoprevention Chittaranjan National Cancer InstituteKolkata 700026India

Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(***)on human acute lymphoblastic leukemia ***:Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms,***,Phallus sp.,Lentinus sp.,Tricholoma sp.,and Serpula *** performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)*** determination,cell cycle profiling,intracellular reactive oxygen species(ROS)and reactive nitrogen species(RNS),and mitochondrial membrane potential were analyzed by flow *** activity of caspases was measured colorimetrically,and the expression pattern of mitochondrial proteins was ***:The methanol extract of *** and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line,*** mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 *** extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 *** methanol extract induced apoptosis by downregulating the expression of Bcl-2,increasing the expression of Bax,and activating the caspase ***:The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.

关键词： Mushroom Astraeus hygrometricus(Pers.)Morgan Apoptosis Antileukemic

新型野生食用菌硬皮地星通过RONS介导线粒体依赖途径诱导人急性淋巴细胞白血病细胞的强凋亡（英文）

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Journal of Traditional Chinese Medical Sciences 2024年第1期 67-77+152页

作者： Amrita Pal Ribhu Ray Anirban Chouni Subhadip Hajra Santanu Paul department of Botany University of Calcutta department of cancer chemoprevention Chittaranjan National Cancer Institute

目标:探讨新型野生食用菌硬皮地星（Astraeus hygrometricus）对人急性淋巴细胞白血病细胞的治疗作用。方法：采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)试验，对5种野生菌类（硬皮地星、竹荪、香菇、口蘑和干朽菌）的提取物... 详细信息

目标:探讨新型野生食用菌硬皮地星（Astraeus hygrometricus）对人急性淋巴细胞白血病细胞的治疗作用。方法：采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)试验，对5种野生菌类（硬皮地星、竹荪、香菇、口蘑和干朽菌）的提取物针对6种癌细胞系和正常细胞的抗增殖及化学预防的潜力进行了广泛筛选。采用流式细胞术分析细胞凋亡、细胞周期、细胞内活性氧(ROS)和活性氮(RNS)以及线粒体膜电位进行检测。采用比色法测定半胱天冬酶活性，分析线粒体蛋白的表达模式。结果：硬皮地星甲醇提取物的抗增殖活性最强，且MOLT-4细胞系最为敏感。菌类提取物可诱导MOLT-4细胞的强选择性凋亡，并在G0/G1期阻滞细胞周期进程。提取物可破坏线粒体膜电位，增强MOLT-4细胞的ROS生成。甲醇提取物通过下调Bcl-2的表达，增加Bax的表达，以及激活caspase级联反应来诱导细胞凋亡。结论：这种新型野生食用菌为抗白血病药物的开发提供了潜在的生物分子库。

关键词：菌类硬皮地星细胞凋亡抗白血病

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

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BIOCELL 2024年第6期48卷 923-934页

作者： BINGJIE LI WENBO CAO JINJING XIAO YIXIAO CHEN QIYING WEI MINGJIN YUE SAIJUN MO department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina Collaborative Innovation Center of Henan Province for cancer chemoprevention ZhengzhouChina State Key Laboratory of Esophageal cancer Prevention and Treatment ZhengzhouChina department of Research and Development Henan Tianxing Education and Media Company LimitedZhengzhouChina

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,inﬁltrating distant regions devoid of lymphatic or vascular *** often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of *** its clinical signiﬁcance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of speciﬁc and efﬁcacious diagnostic and therapeutic *** the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-speciﬁc expression proﬁles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and *** the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as inﬂuential players in *** involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic *** study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in *** comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

关键词： Perineural invasion Non-coding RNA Diagnose and treatment cancer Biomarker

Protein translation:biological processes and therapeutic strategies for human diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1048-1064页

作者： Xuechao Jia Xinyu He Chuntian Huang Jian Li Zigang Dong Kangdong Liu department of Pathophysiology School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450000China China-US(Henan)Hormel cancer Institute ZhengzhouHenan 450000China department of Pathology and Pathophysiology Henan University of Chinese MedicineZhengzhouHenan 450000China Tianjian Laboratory of Advanced Biomedical Sciences ZhengzhouHenan 450052China Research Center for Basic Medicine Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052 HenanChina Provincial Cooperative Innovation Center for cancer chemoprevention Zhengzhou UniversityZhengzhouHenan 450000China State Key Laboratory of Esophageal cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenan 450000China The Collaborative Innovation Center of Henan Province for cancer chemoprevention ZhengzhouHenan 450000China

Protein translation is a tightly regulated cellular process that is essential for gene expression and protein *** deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human *** this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease *** explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome *** translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease *** development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation ***,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular ***,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is *** conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic *** in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human ***,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.

关键词： translation offering precise

Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3205-3217页

作者： Bing-Chen Zhang Chun-Mei Lai Bang-Yue Luo Jing-Wei Shao Fujian Provincial Key Laboratory of cancer Metastasis chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350116China department of Laboratory Medicine Dongguan Institute of Clinical Cancer Researchthe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523058China College of Materials and Chemical Engineering MinjiangUniversityFuzhou350108China

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)***,combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted ***,based on a universal triterpene template and the anticancer active agent ursolic acid(UA),a cytomembrane-coated biomimetic delivery nanoplatform(UR@M)prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma(HCC)***@M showed enhanced tumor accumulation in vivo with homologous tumor targeting,and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target *** activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway,which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of *** strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor ***,the UA-templated strategy“killed three birds with one stone”by establishing a self-assembly nanosystem,inducing tumor cell death,and promoting synergistic immunostimulation for HCC treatment.

关键词： Ursolic acid Self-assembly Biomimetic nanoplatform Hepatocellular carcinoma CRISPR/Cas9 Immune checkpoint blockade Gene therapy Immunotherapy

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

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Frontiers of Medicine 2023年第2期17卷 290-303页

作者： Yubing Zhou Xinyu He Yanan Jiang Zitong Wang Yin Yu Wenjie Wu Chenyang Zhang Jincheng Li Yaping Guo Xinhuan Chen Zhicai Liu Jimin Zhao Kangdong Liu Zigang Dong The Pathophysiology department School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhou 450000China The China-US(Henan)Hormel cancer Institute Zhengzhou 450000China State Key Laboratory of Esophageal cancer Prevention and Treatment Zhengzhou 450000China Provincial Cooperative Innovation Center for cancer chemoprevention Zhengzhou UniversityZhengzhou 450000China cancer chemoprevention International Collaboration Laboratory Zhengzhou 450000China Oncology department The Tumor Hospital of Linzhou CityLinzhou 456500China

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine cyclin-dependent kinase 2 patient-derived xenograft esophageal squamous cell carcinoma

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Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1874-1888页

作者： Penglei Wang Xuechao Jia Bingbing Lu Han Huang Jialin Liu Xuejiao Liu Qiong Wu Yamei Hu Pan Li Huifang Wei Tingting Liu Dengyun Zhao Lingwei Zhang Xueli Tian Yanan Jiang Yan Qiao Wenna Nie Xinli Ma Ruihua Bai Cong Peng Zigang Dong Kangdong Liu department of Pathophysiology Basic Medicine Research CenterSchool of Basic Medical SciencesAMSZhengzhou University450000 ZhengzhouChina China-US(Henan)Hormel cancer Institute 450000 ZhengzhouChina The department of Pathology Affiliated Cancer Hospital of Zhengzhou University450000 ZhengzhouChina The department of Dermatology Xiangya HospitalCentral South University410078 ChangshaChina The Collaborative Innovation Center of Henan Province for cancer chemoprevention 450000 ZhengzhouChina State Key Laboratory of Esophageal cancer Prevention and Treatment Zhengzhou University450000 ZhengzhouChina Provincial Cooperative Innovation Center for cancer chemoprevention Zhengzhou UniversityZhengzhouChina

Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic *** of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising *** this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS *** enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/*** assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase ***,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase ***,erianin attenuated melanoma and colorectal cancer in ***,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.

关键词： MEK1/2 BRAF activation

Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

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Journal of Chinese Pharmaceutical Sciences 2016年第1期25卷 12-22页

作者： Sujit Nair Ah-Ng Tony Kong Amrita cancer Discovery Biology Laboratory Amrita Vishwa Vidyapeetham University Center for cancer chemoprevention Research and department of Pharmaceutics Rutgers The State University of New Jersey

Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.

关键词： Pharmacometrics Pharmacokinetics Quantitative systems pharmacology Target engagement Metabolism Pharmacogenomics chemoprevention Sulforaphane Isothiocyanate Prostate cancer

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Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth in vitro and patient-derived xenografts in vivo

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4122-4137页

作者： Fanxiang Yin Ran Zhao Dhilli Rao Gorja Xiaorong Fu Ning Lu Hai Huang Beibei Xu Hanyong Chen Jung-Hyun Shim Kangdong Liu Zhi Li Kyle Vaughn Laster Zigang Dong Mee-Hyun Lee department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China China-US(Henan)Hormel cancer Institute Zhengzhou 450008China Translational Medical Center the First Affiliated Hospital of Zheng zhou UniversityZhengzhou 450052China The Hormel Institute University of MinnesotaAustinMN 55912USA department of Biomedicine Health&Life Convergencen ScienceBK21 FourCollege of Pharmacy Mokpo National UniversityJeonnam 58554Republic of Korea The Collaborative Innovation Center of Henan Province for cancer chemoprevention Zhengzhou 450001China department of General Surgery the Affiliated Tumor Hospital of Zhengzhou UniversityZhengzhou 450008China College of Korean Medicine Dongshin UniversityNaju 58245Republic of Korea

Colorectal cancer(CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1(PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration,and apoptosis. Fibroblast growth factor receptor 1(FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However,the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATPdependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48inhibited cell proliferation in CRC cells(HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft(PDX) murine tumor models,we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC.

关键词： PIM1 FGFR1 Colorectal cancer HCI-48 Targeted therapy Small moleculecompound ofchalcone Patient-derived xenograft model ATPKinase activity

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Targets and molecular mechanisms of a citrus flavonoid, hesperidin, against luminal breast cancer cells: an integrative bioinformatics analysis

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Asian Pacific Journal of Tropical Biomedicine 2019年第12期9卷 531-538页

作者： Adam Hermawan Herwandhani Putri department of Pharmaceutical Chemistry Faculty of PharmacyUniversitas Gadjah MadaSekip Utara Ⅱ55281 YogyakartaIndonesia cancer chemoprevention Research Center Faculty of PharmacyUniversitas Gadjah MadaSekip Utara Ⅱ55281 YogyakartaIndonesia

Objective:To identify the potential target and mechanisms of hesperidin in MCF-7 estrogen receptor-positive breast cancer cells using bioinformatics ***:Gene expression profiles were accessed from public database *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was carried out with Database for Annotation,Visualization and Integrated *** protein-protein interaction network was analyzed by STRING-DB and visualized by *** factor regulatory networks were constructed from TRED,TRRUST,Reg Network and visualized by *** association analysis was conducted by Web ***:GO and KEGG pathway enrichment analysis revealed biological processes,cellular components and molecular functions that were related to cancer and estrogen signaling *** pathway enrichment analysis of the genes in transcription factor-differential expression genes regulatory network showed regulation of cancer,estrogen signaling pathways,epidermal growth factor receptor tyrosine kinase inhibitor resistance,and endocrine ***,drug association analysis revealed that hesperidin affected the expression of the same gene as ***:Hesperidin targets estrogen receptor signaling in estrogen receptor-positive breast cancer *** of this study could trace the molecular mechanism of hesperidin in estrogen receptor-positive breast cancer cells and integrative bioinformatics analysis could accelerate drug discovery and development.

关键词： Hesperidin Breast cancer Bioinformatics Estrogen receptor Signaling pathway