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Phase separation of Nur77 mediates XS561-induced apoptosis by promoting the formation of Nur77/Bcl-2 condensates

Acta Pharmaceutica Sinica B 2024年第3期14卷 1204-1221页

作者： Xiaohui Chen Meichun Gao Yongzhen Xia Xin Wang Jingbo Qin Hongying He Weirong Liu Xiaowei Zhang Shuangzhou Peng Zhiping Zeng Ying Su Xiaokun Zhang School of Pharmaceutical Science Fujian Provincial Key Laboratory of Innovative Drug Target ResearchXiamen UniversityXiamen 361002China NucMito Pharmaceuticals Co. Ltd.Xiamen 361000China Department of Clinical laboratory the Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

The orphan nuclear receptor Nur77 is a critical regulator of the survival and death of tumor *** pro-death effect of Nur77 can be regulated by its interaction with Bcl-2,resulting in conversion of Bcl-2 from a survival to *** Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy,targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer ***,we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 *** vitro and animal studies revealed an apoptotic effect of XS561 in a range of tumor cell lines including MDA-MB-231 triple-negative breast cancer(TNBC)and MCF-7/LCC2 tamoxifen-resistant breast cancer(TAMR)in a Nur77-dependent *** studies showed XS561 potently induced the translocation of Nur77 from the nucleus to mitochondria,resulting in mitochondria-related ***,XS561-induced accumulation of Nur77 at mitochondria was associated with XS561 induction of Nur77 phase separation and the formation of Nur77/Bcl-2 ***,our studies identify XS561 as a new activator of the Nur77/Bcl-2 apoptotic pathway and reveal a role of phase separation in mediating the apoptotic effect of Nur77 at mitochondria.

关键词： XS561 Nur77 Bcl-2 Apoptosis Mitochondria Phase separation TNBC TAMR

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Gold-based nanomaterials for the treatment of brain cancer

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Cancer Biology & Medicine 2021年第2期18卷 372-387页

作者： Li Tu Zheng Luo Yun-Long Wu Shuaidong Huo Xing-Jie Liang fujian provincial key laboratory of innovative drug target research School of Pharmaceutical SciencesXiamen UniversityXiamen 361102China CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China

Brain cancer,also known as intracranial cancer,is one of the most invasive and fatal cancers affecting people of all *** the great advances in medical technology,improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier(BBB).Fortunately,recent endeavors using gold-based nanomaterials(GBNs)have indicated the potential of these materials to cross the ***,GBNs might be an attractive therapeutic strategy against brain ***,we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer ***,the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized,with an emphasis on the mechanism of their effective BBB ***,the challenges and future outlook in using GBNs for brain cancer treatment are *** hope that this review will spark researchers'interest in constructing more powerful nanoplatforms for brain disease treatment.

关键词： Gold-based nanomaterials BBB penetration brain cancer therapy

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Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1170-1183页

作者： Xudong Zhao Yudan Wang Haoming Xia Shuqiang Liu Ziyue Huang Risheng He Liang Yu Nanfeng Meng Hang Wang Junqi You Jinglin Li Judy Wai Ping Yam Yi Xu Yunfu Cui Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina key laboratory of Basic Pharmacology of Ministry of Education Zunyi Medical UniversityZunyiGuizhouChina key laboratory of Functional and Clinical Translational Medicine Fujian Province UniversityXiamen Medical CollegeXiamenFujianChina Jiangsu Province Engineering research Center of Tumor targeted Nano Diagnostic and Therapeutic Materials Yancheng Teachers UniversityYanchengJiangsuChina key laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province HangzhouZhejiangChina key laboratory of Gastrointestinal Cancer(fujian Medical University) Ministry of EducationSchool of Basic Medical SciencesFujian Medical UniversityFuzhouFujianChina State key laboratory of Chemical Oncogenomics Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhenGuangdongChina key laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou Department of PharmacyChangxing People’s HospitalChangxingZhejiangChina

Hepatocellular carcinoma(HCC)being a leading cause of cancer-related death,has high associated mortality and recurrence *** has been of great necessity and urgency to find effective HCC diagnosis and treatment *** have shown that microvascular invasion(MVI)is an independent risk factor for poor prognosis after *** abnormal expression of biomacromolecules such as circ-RNAs,lncRNAs,STIP1,and PD-L1 in HCC patients is strongly correlated with *** of several markers mentioned in this review affects the proliferation,invasion,metastasis,EMT,and anti-apoptotic processes of HCC cells through multiple complex ***,these biomarkers may have an important clinical role and serve as promising interventional targets for *** this review,we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

关键词： Hepatocellular carcinoma Microvascular invasion Biomarkers Progress Molecular mechanism

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Biological investigation of phenyl benzoate, benzophenone, and xanthone compounds

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Journal of Chinese Pharmaceutical Sciences 2022年第10期31卷 738-745页

作者： Beidou Zhou Chun Lei Xuemei Liao Hang Zhu Zhipeng Ruan Yuanyuan Fang Guifen Xu Yuli Chen School of Pharmacy and Medical Technology Putian UniversityKey Laboratory of Pharmaceutical Analysis and Laboratory Medicine(Putian University)Fujian Provincial UniversityPutian 351100China School of Pharmacy FujianMedical UniversityFuzhou350108China fujian Tianquan Pharmaceutical Co. Ltd.Longyan 364000China

In the present study, we evaluated the antitumor, anti-tyrosinase, anti-pancreatic lipase, antibacterial, antifungal, and anti-α-glycosidase activities for all or a subset of 20 known compounds. They included 8 phenyl benzoates, 10 benzophenones, and 2 xanthones. Phenyl benzoate compounds 1–8 did not exhibit evident antitumor activity, which was consistent with existing theories. Compounds 16, 17, and 18 exhibited moderate anti-tyrosinase activity. In addition, compounds 11 and 18 exhibited moderate inhibitory activity against Candida albicans, and compound 20 exhibited stronger anti-α-glycosidase activity than quercetin, with an IC_(50)of approximately 2.45 μM. These results demonstrated that compounds 11, 16–18, and 20 were promising leads for further structural modification.

关键词： Phenyl benzoate Benzophenone Xanthone Antibacterial Antifungal α-Glycosidase

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