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Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin b-mediated pyroptosis of prostate cancer cells

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Asian Pacific Journal of Tropical biomedicine 2024年第2期14卷 55-64页

作者： Xu-Yun Wang Wen-Jing Xu bo-Nan Li Tian-Song Sun Wen Sheng Department of Andrology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Dermatology The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha410021China School of Integrated Chinese and Western Medicine Hunan University of Chinese MedicineChangsha410208China Andrology Laboratory Hunan University of Chinese MedicineChangsha410208China School of Rehabilitation Medicine and Health Care Hunan University of MedicineHuaihua418000China School of Traditional Chinese Medicine Hunan University of MedicineHuaihua418000China

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying ***:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and *** expression was analyzed using monodansylcadaverine *** and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR *** damage was examined using the lactate dehydrogenase ***,cathepsin b and NLRP3 were detected by ***:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of *** levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus *** changes were reversed upon overexpression of ***,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol *** cathepsin b reversed the regulatory effects of icariin plus ***:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin *** findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

关键词： Icariin Curcumol Autophagy mTOR cathepsin b Pyroptosis Prostate cancer

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清解扶正颗粒调控cathepsin b/NLRP3通路减轻大肠癌小鼠5-FU化疗性肠黏膜炎的机制研究

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康复学报 2024年

作者：袁颖绯林久茂林明和赵锦燕陈旭征刘锦洪朱晓勤福建省中西医结合老年性疾病重点实验室福建省高校中西医结合基础重点实验室福建中医药大学中西医结合研究院

目的基于cathepsin b/NLRP3通路探讨清解扶正颗粒对大肠癌小鼠经5-氟尿嘧啶（5-FU）化疗后所致的肠黏膜炎的治疗作用及作用机制。方法将24只雄性bALb/c小鼠采取右前肢腋部皮下接种CT26细胞的方法构建大肠癌皮下移植瘤小鼠模型，待瘤... 详细信息

目的基于cathepsin b/NLRP3通路探讨清解扶正颗粒对大肠癌小鼠经5-氟尿嘧啶（5-FU）化疗后所致的肠黏膜炎的治疗作用及作用机制。方法将24只雄性bALb/c小鼠采取右前肢腋部皮下接种CT26细胞的方法构建大肠癌皮下移植瘤小鼠模型，待瘤体生长至100-300 mm3时，按照瘤体体积将小鼠随机分为对照组（Control组）、5-FU组、5-FU+清解扶正颗粒组（5-FU+QFG组），每组8只。对照组给予生理盐水灌胃和腹腔注射，其他每组小鼠腹腔注射5-FU(50 mg/kg·d-1)每日1次，连续5 d;5-FU+QFG组在化疗的同时灌胃给予清解扶正颗粒（1.0 g/kg·d-1），每日1次，连续7 d。每天观察小鼠的腹泻情况，记录体质量及瘤体积等情况。第7 d末次给药后禁食12 h，动物取材，进行实验检测。HE染色观察小鼠空肠组织病理变化；ELISA法检测各组小鼠血清中二胺氧化酶（DAO）、D-乳酸（D-LA）、内毒素（ET）、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)表达；免疫组化检测空肠组织中组织蛋白酶b(cathepsin b)的阳性表达；实时荧光定量PCR法检测空肠组织中紧密连接蛋白ZO-1、Occludin mRNA的表达，Western blot检测空肠组织中ZO-1、Occludin、cathepsin b、NLRP3、ASC、cleaved Caspase-1蛋白的表达。结果在实验周期内，清解扶正颗粒能够显著减轻5-FU化疗引起的腹泻症状（P0.05），对5-FU抑制瘤体生长没有显著的协同效应（P>0.05）；清解扶正颗粒可显著改善5-FU化疗引起的肠黏膜绒毛变短、隐窝变深、炎性细胞浸润等肠黏膜损伤症状；与5-FU组比较，清解扶正颗粒可以显著降低大肠癌小鼠血清中DAO、D-LA、ET以及促炎细胞因子TNF-α、IL-1β、IL-6的含量（Pcathepsin b蛋白的表达（Pcathepsin b/NLRP3通路，减少促炎细胞因子释放，抑制肠黏膜炎症反应，修复肠黏膜屏障损伤，从而减轻5-FU引起的化疗性肠黏膜炎。

关键词：清解扶正颗粒 5-氟尿嘧啶肠黏膜炎 cathepsin b NLRP3

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cathepsin b-responsive prodrugs for cancer-targeted therapy:Recent advances and progress for clinical translation

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Nano Research 2022年第8期15卷 7247-7266页

作者： Seong Ik Jeon Suah Yang Man Kyu Shim Kwangmeyung Kim biomedical Research Institute Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea

The cathepsin b-responsive prodrugs are promising strategies to reduce the serious adverse effects of anticancer drugs by improving the cancer selectivity that can be specifically activated by overexpressed cathepsin b in targeted cancer ***,clinical translation of such therapeutic approaches has been restricted by low antitumor efficacy that is mainly attributable to undesirable pharmacokinetic profiles and inefficient tumor-targeting of cathepsin b-responsive prodrugs,due to their small-molecule *** recent decades,many researchers have widely investigated the drug delivery system(DDS)to improve the in vivo pharmacokinetic profiles and tumor-targeting efficiency of cathepsin b-responsive prodrugs via the application of polymers,dendrimers,antibodies,lipids,and inorganic nanoparticles as drug *** addition,the potential therapeutic efficacy of DDS for cathepsin b-responsive prodrugs is demonstrated in multiple studies and combinatorial treatment with typical therapeutic modalities can effectively overcome the challenges of tumor heterogeneity and multidrug *** this review,recent advances and progress of new DDS for cathepsin b-responsive prodrugs are outlined,and their clinical trials are ***,potential challenges and the outlooks for clinical translation of cathepsin b-responsive prodrugs are highlighted.

关键词： cathepsin b prodrug chemotherapy drug delivery system targeted cancer therapy

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cathepsin b protease is required for metamorphism in silkworm, bombyx moil

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Insect Science 2008年第3期15卷 201-208页

作者： Gen-Hong Wang Chun Liu Qing-You Xia Xing-Fu Zha Jie Chen Liang Jiang Key Sericultural Laboratory of the Agricultural Ministry College of Biotechnology Southwest University Chongqing China

cathepsin b belongs to lysosomal cysteine protease of the papain family. Temporal and spatial expression analysis of cathepsin b of bombyx mori （bmCtb） was carried out based on Expression Sequence Tags （ESTs） data, oligonucleotide microarray, reverse transcription polymerase chain reaction （RT-PCR） and quantitative real-time PCR. Expression of bmCtb was observed in all of the tissues and stages. Among the 10 tested tissues, the fat body and posterior silk gland are the two most enriched tissues with bmCtb. During bombyx development, there was an expression fastigium of bmCtb during metamorphosis. RNA interference was used to suppress the expression of cathepsin b during metamorphosis. Significant developmental defective phenotypes were obtained in the RNAi treated group. The dramatically reduced expression of bmCtb was con^rmed by Northern blot and quantitative real-time PCR. These evidences strongly suggest cathepsin b proteinase was predominantly involved in the metabolism process of fat body and the posterior silk gland and was critical for metamorphism and development of silkworm, bombyx mori.

关键词： cathepsin b RNA interference quantitative real-time PCR bombyx mori

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cathepsin b-responsive nanodrug delivery systems for precise diagnosis and targeted therapy of malignant tumors

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Chinese Chemical Letters 2020年第12期31卷 3027-3040页

作者： Yanan Li Ting Mei Shupeng Han Tao Han Yongbing Sun Hui Zhang Feifei An Department of Radiology First Hospital of Shanxi Medical UniversityTaiyuan 030001China College of Medical Imaging Shanxi Medical UniversityTaiyuan 030001China Institute of Medical Engineering Department of Biophysicschool of Basic Medical ScienceHeatih Science Center Xi'an Jiaotong UniverstyXi'an 710061China College of Chemistry and Life Science Institute of Functional MoleculesChengdu Normal UniversityChengdu 611130China Division of Pharmaceutics National Pharmaceutical Engineering Center for Solid Preparation in Chinese Hierbal MedicimeJiamgpri Unverity of Truditional Chinese MedicinveNanchang 330006China

The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic *** biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic *** booming nanotechnology field has realized the importance of cathepsin b to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical *** this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin b,the outstanding achievements of cathepsin b-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically ***,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.

关键词： Tumor microenvironment cathepsin b Theranostics Precise diagnosis Targeted therapy

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cathepsin b EXPRESSION AND ITS RELATIONSHIP WITH MICROVESSEL DENSITY AND bIOLOGICAL bEHAVIOUR OF COLORECTAL CARCINOMA

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Chinese Journal of Cancer Research 2002年第4期14卷 293-296页

作者： WANG Ya-lan王娅兰 LIN Xiao林晓 Department of Pathology Chongqing University of Medical Sciences Chongqing 400016 Department of Pathology Chongqing University of Medical Sciences Chongqing 400016

Objective: To investigate cathepsin b(Cb) expression in colorectal carcinoma and its relationship with microvessel density (MVD) and biological behavior. Methods: Cb and MVD were detected by immunohistochemistry in 47 cases of colorectal carcinoma. Results: The expression of Cb in mucinous colorectal carcinoma was significantly higher than that in no-mucinous colorectal carcinoma. There was significant difference (Pb was stronger than that in group with negative Cb. There was also significant difference (Pb expression has correlation with MVD, invasion and metastasis in colorectal carcinoma, especially in mucinous colorectal carcinoma.

关键词： Colorectal carcinoma cathepsin b Invasion Metastasis Angiogenesis

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cathepsin b antisense oligodeoxynucleotide suppresses invasive potential of MG-63 cells

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Journal of Pharmaceutical Analysis 2008年第2期20卷 100-103,118页

作者： He M. Xiao Z. Li S. Chen A. Department of Spinal Surgery Guangxi Medical University Nanning 530021 China Department of Orthopaedics Tongji Hospital Tongji Medical College Wuhan 430030 China

Objective To study the biological effects of cathepsin b phosporothioated antisense oligodeoxynucleotide on human osteosarcoma cell line MG-63 after *** A 18-mer phosphorothioate antisense oligodeoxynucleotide(ASODN)targeted against the cathepsin b mRNA was transfected into the human osteosarcoma cell line MG-63 by lipofectamine *** sense and nonsense oligodeoxynucleotides to cathepsin b and blank vector were used as *** expression of cathepsin b mRNA was examined by RT-PCR an...

关键词： Antisense oligodeoxynucleotide cathepsin b Invasion RT-PCR

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Changes of cathepsin b in human photoaging skin both in vivo and in vitro

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Chinese Medical Journal 2010年第5期123卷 527-531页

作者： LAI Wei ZHENG Yue YE Zhang-zhang SU Xiang-yang WAN Miao-jian GONG Zi-jian XIE Xiao-yuan LIU Wei Department of Dermatovenereology Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510630 China Department of Dermatology General Hospital of Air Force of the Chinese People's Liberation Army Beijing 100142 China

background cathepsin b plays an important role tumorigenesis： whether it plays a role in photoaged skin cathepsin b in skin photoaging in vivo and in vitro. n cell cycle, extracellular matrix changes and cutaneous remains unknown. This study aimed to investigate the role of Methods The expressions of cathepsin b were compared with immunohistochemical methods in solar exposed skin and solar protected skin of six healthy Chinese volunteers. The mRNA and protein expression of cathepsin b in ultraviolet light A （UVA） induced premature senescence fibroblasts in vitro were detected by real-time reverse transcription polymerase chain reaction （RT-PCR） and Western blotting technique. Results Decreased expression of cathepsin b was observed in photoaged skin compared with that of the solar protected skin. In the UVA induced, premature senescence fibroblasts, a lower expression of cathepsin b was detected by Western blotting and a decreased synthesis of cathepsin b mRNA in the same cells was revealed by real-time RT-PCR. Conclusions The results demonstrated a significant negative correlation between skin photoaging and cathepsin b in vitro and in vivo. We propose that cathepsin b, besides matrix metalloproteinases and antioxidant enzymes, is involved in the process of skin photoaging in that it contributes to extracellular matrix remodelling and is a dominant protease in cellular apoptosis and senescence.

关键词： cathepsin b ultraviolet light photoaging skin

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Catechu Inhibiting cathepsin b Activity and Motility of HT1080 Cells

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Chemical Research in Chinese Universities 2011年第2期27卷 269-272页

作者： YUAN Hao YANG Jin-gang WANG Zhong-yuan ZHAO Shu-hua YU Da-hai FANG Xue-xun Key Laboratory of Molecular Enzymology and Engineering Ministry of Education College of Life Science Jilin University Changchun 130012 P. R. China Department of Traditional Chinese Medicine China-Japan Union Hospital of Jilin University Changchun 130041 P R. China

We reported that Catechu extract has a significant inhibitory effect on cathepsin b activity. The IC50 value for the Catechu extract against cathepsin b was 7.6 μg/mL. In addition, we showed that HT1080 human fibrosarcoma cells express cathepsin b and Catechu modulate the invasion and motility of these cells. These data may provide molecular mechanisms for the therapeutic effects of Catechu.

关键词： cathepsin b Traditional Chinese medicine Catechu Tumor Cell invasion Cell motility

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S53G SNP in cathepsin b: Can be Used as a Molecular biomarker to breast Cancer?

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Open Journal of Genetics 2022年第4期12卷 43-56页

作者： Letícia Cristina Dalzy Castro Danielle Queiroz Calcagno Carlos Eduardo de Melo Amaral Luiz Carlos Santana da Silva Programa de Pós-graduaç ã o em Oncologia e Ciências Médicas Universidade Federal do Pará Belém Brasil Laboratório de Erros Inatos do Metabolismo Universidade Federal do Pará Belém Brasil Núcleo de Pesquisa em Oncologia Universidade Federal do Pará Belém Brasil Fundaç ã o Centro de Hematologia e Hemoterapia do Pará Belém Brasil

cathepsin b (CTS b) is a proteolytic enzyme that participates in several important biological processes. However, when it is altered can be involved in development of breast cancer, a disease with high incidence and mortality rate among women. Many studies have shown a correlation between high CTS b expression and breast tumor. Furthermore, it has been shown that the SNP rs1803250 (S53G) leads to structural and functional changes in protein that can make it pathogenic. The present study aimed to evaluate a possible association of SNP rs1803250 (S53G) with breast cancer. For this, real-time PCR was performed on a sample collected in the State of Pará, with 127 patients and 122 controls. The SNP frequency in this region was 0.12, according to a research project in progress that aims to identify Amerindians molecular alterations. This indicates that the SNP is found in region with a distribution close to worldwide frequency of 0.09. Our results showed that the SNP was in Hardy-Weinberg Equilibrium in collected sample, but C variant allelic frequency was 0.08 in both patients and control groups, which is extremely similar to global average. Moreover, homozygotes CC was not found in the sample and SNP genotypes frequency in patients and control groups was not significantly different. In addition, statistical analysis showed that the SNP did not have to correlate with tumor subtypes nor with tumor staging. Therefore, according to the analyzed sample, the SNP rs1803250 has no association with breast cancer and it cannot be considered a molecular biomarker for breast cancer.

关键词： cathepsin b Polymorphism breast Cancer

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