Article
Chemistry, Multidisciplinary
Suresh Udutha, Roshan M. Borkar, G. Shankar, T. Sony, Aishwarya Jala, E. Vamshi Krisna, T. Kiran Kumar, S. Misra, S. Prabhakar, R. Srinivas
Summary: Bortezomib (BTZ) is a potent reversible inhibitor of proteasome used in the treatment of multiple myeloma. Studies on its degradation under various conditions identified 16 degradation products, with some showing toxicity in vitro cell toxicity tests. Further in silico studies suggested potential hepatotoxicity and genotoxicity of BTZ and its degradation products.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Harriet Ghansah, Ildiko Beke Debreceni, Zsolt Fejes, Bela Nagy, Janos Kappelmayer
Summary: The study revealed that Bortezomib (BTZ) induces a procoagulant platelet phenotype, leading to increased phosphatidylserine (PS) and P-selectin expression levels, as well as depolarization of mitochondrial inner membrane potential in gel-filtered platelets (GFPs) compared to platelet-rich plasma (PRP). The presence of plasma proteins in PRP may attenuate the procoagulant effect of BTZ on platelets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Jianhao Liu, Ruogang Zhao, Xiaowen Jiang, Zhaohuan Li, Bo Zhang
Summary: Bortezomib is a proteasome inhibitor that has been approved for the treatment of multiple myeloma and other hematological cancers. However, its limited specificity, poor permeability, and low bioavailability hinder its applications. Recent research has focused on the development of BTZ-based drug delivery systems.
Article
Biochemistry & Molecular Biology
Kyota Ishii, Mayuko Hido, Misaki Sakamura, Nantiga Virgona, Tomohiro Yano
Summary: This study demonstrated that T3, TOS, and T3E enhance the sensitivity of the proteasome inhibitor BTZ in solid cancers by modulating the activity of NFE2L1. Inactivation of NFE2L1 by T3, TOS, and T3E is essential to potentiate the cytotoxic effect of BTZ in solid cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Camille Schlesser, Thomas Meul, Georgios Stathopoulos, Silke Meiners
Summary: The anti-diabetic drug metformin induces resistance of cancer cells to the proteasome inhibitor Bortezomib by impairing the activity and assembly of the 26S proteasome complexes.
Review
Immunology
Naeemeh Khalesi, Shahla Korani, Mitra Korani, Thomas P. Johnston, Amirhossein Sahebkar
Summary: Autoimmune diseases are conditions where the immune system cannot distinguish self from non-self, leading to tissue injury. The proteasome inhibitor bortezomib has shown effectiveness in treating patients with ADs resistant to conventional therapies.
INFLAMMOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Mingyu Chen, Sarun Juengpanich, Shijie Li, Win Topatana, Ziyi Lu, Qiang Zheng, Jiasheng Cao, Jiahao Hu, Esther Chan, Lidan Hou, Jiang Chen, Fang Chen, Yu Liu, Sukanda Jiansirisomboon, Zhen Gu, Suparat Tongpeng, Xiujun Cai
Summary: This study reports on a targeted therapy for gallbladder cancer using pH-responsive nanoparticles encapsulating bortezomib and mediated by estrogen-induced endocytosis. The treatment effectively inhibits proteasomes and induces apoptosis under tumor microenvironment and laser irradiation.
Article
Cell Biology
Mohummad Aminur Rahman, Agnete S. T. Engelsen, Shahin Sarowar, Christian Bindesboll, Even Birkeland, Dorota Goplen, Maria L. L. Lotsberg, Stian Knappskog, Anne Simonsen, Martha Chekenya
Summary: The study found that bortezomib can enhance the efficacy of temozolomide by inhibiting autophagic flux, thereby increasing the treatment effect on glioblastoma and increasing the occurrence of cell apoptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Guangtao Gao, Yong Xu, Jingjing Gan, Xinya Cao, Xiaoqing Dong, Mengkun Fang, Ying Du, Peipei Xu, Junyi Che, Bing Chen
Summary: This study reports a targeting strategy for multiple myeloma using platelet membrane-coated nanoparticles encapsulating BTZ. Compared to non-targeted BTZ, the nanoparticle system shows significant improvements in selectivity, cellular uptake, and anticancer effects, demonstrating a high potential for multiple myeloma patients.
Article
Pharmacology & Pharmacy
Xiuhui Chen, Yanhong Chen, Yitao Ou, Wenjie Min, Shuli Liang, Lei Hua, Yinghua Zhou, Cheng Zhang, Peifeng Chen, Zhongjin Yang, Wenhui Hu, Ping Sun
Summary: The abnormal activation of NLRP3 inflammasome is important in the pathogenesis of psoriasis. Bortezomib, a marketed drug for treating multiple myeloma, specifically inhibits NLRP3 inflammasome activation and may be a potential therapeutic drug for psoriasis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Maria V. Yusenko, Abhiruchi Biyanee, Mattias K. Andersson, Silke Radetzki, Jens P. von Kries, Goran Stenman, Karl-Heinz Klempnauer
Summary: Studies on MYB in human malignancies have identified it as a potential drug target for AML and ACC. While transcription factors are often considered hard to target, recent developments have shown successful targeting of MYB with low molecular weight compounds. The use of proteasome inhibitors to suppress oncogenic MYB activity opens up new possibilities for therapeutic approaches in MYB-driven cancers.
Article
Oncology
Roghaye Hamidi, Farangis Ataei, Saman Hosseinkhani
Summary: Dysfunction in the apoptotic signaling pathway is closely associated with various diseases, including cancer. Understanding the regulatory points underlying cancer-related death can help in the development of new strategies to overcome clinical challenges. In this study, the effects of proteasome inhibitor Bortezomib and calpain inhibitor ALLN on protein levels of caspase-3, caspase-9, XIAP, and E3-ligase PARC were investigated in HEK293T cells. Both inhibitors resulted in ATP depletion and caspase-3 activation, leading to cell death. Western blot analysis showed that both ALLN and Bortezomib inhibited degradation of XIAP, while only ALLN inhibited caspase proteolytic degradation. Additionally, treatment with the inhibitors increased the level of E3-ligase PARC. These findings suggest that inhibition of proteasome and calpains promotes cell death by modulating the levels of apoptotic proteins.
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Biochemistry & Molecular Biology
Hui Li, Mridul Roy, Long Liang, Wenjie Cao, Bin Hu, Yanan Li, Xiaojuan Xiao, Haiqin Wang, Mao Ye, Shuming Sun, Bin Zhang, Jing Liu
Summary: This study identified the deubiquitylase USP12 plays an important role in pro-survival autophagy and drug resistance in multiple myeloma by stabilizing HMGB1 protein. The USP12/HMGB1 axis might be a potential diagnostic and therapeutic target in human MM.
Article
Oncology
Gregoire Quinet, Wendy Xolalpa, Diana Reyes-Garau, Nuria Profitos-Peleja, Mikel Azkargorta, Laurie Ceccato, Maria Gonzalez-Santamarta, Maria Marsal, Jordi Andilla, Fabienne Aillet, Francesc Bosch, Felix Elortza, Pablo Loza-Alvarez, Brigitte Sola, Olivier Coux, Rune Matthiesen, Gael Roue, Manuel S. Rodriguez
Summary: The research identified an enrichment of autophagy-lysosome system (ALS) components in bortezomib (BTZ)-resistant cells in mantle cell lymphoma (MCL) patients. By blocking proteaphagy, the normal proteasomal activity was reactivated and the BTZ antitumor effect was restored in vitro and in vivo models of BTZ resistance. These findings suggest a proteolytic switch from the ubiquitin-proteasome system (UPS) to ALS in B-cell lymphoma refractory to proteasome inhibition, opening up new therapeutic avenues for treatment-resistant tumors.
Correction
Oncology
Abedul Haque, Mohammad Aminur Rahman, James R. Fuchs, Zhuo Chen (Georgia), Fadlo R. Khuri, Dong M. Shin, A. R. M. Ruhul Amin
Article
Oncology
Taofeek K. Owonikoko, Bhakti Dwivedi, Zhengjia Chen, Chao Zhang, Benjamin Barwick, Vinicius Ernani, Guojing Zhang, Melissa Gilbert-Ross, Jennifer Carlisle, Fadlo R. Khuri, Walter J. Curran, Andrey A. Ivanov, Haian Fu, Sagar Lonial, Suresh S. Ramalingam, Shi-Yong Sun, Edmund K. Waller, Gabriel L. Sica
Summary: This study identified four subtypes of SCLC using RNA sequencing and immunohistochemistry, with the SCLC-Y subtype associated with an inflamed phenotype and favorable prognosis. Upregulation of interferon-gamma response genes was observed in long-term survivors, with higher expression in patients of the SCLC-Y subtype.
JOURNAL OF THORACIC ONCOLOGY
(2021)
Correction
Oncology
Kaisheng Mao, Fakeng Liu, Xiuju Liu, Fadlo R. Khuri, Adam Marcus, Mingsong Li, Wei Zhou
Editorial Material
Oncology
Fadlo R. Khuri
Summary: The COVID-19 pandemic has brought attention to health and vaccine disparities, and the collaborative development of targeted therapies for lung cancer has shown a promising path forward for improving survival rates.
Article
Oncology
Arafat H. Tfayli, Pierre M. Sfeir, Bassem Y. Youssef, Fadlo R. Khuri
CA-A CANCER JOURNAL FOR CLINICIANS
(2021)
Editorial Material
Oncology
Fadlo R. Khuri
Editorial Material
Oncology
Suresh S. Ramalingam, Fadlo R. Khuri
Article
Oncology
Fadlo R. Khuri
Article
Chemistry, Multidisciplinary
Wen-die Wang, Yue Shang, Chen Wang, Jun Ni, Ai-min Wang, Gao-jie Li, Ling Su, Shu-zhen Chen
Summary: This study investigated the effects of c-FLIP on the expression and ubiquitination levels of FoxM1 in non-small-cell lung cancer (NSCLC) cells, and explored the role of c-FLIP/FoxM1 in drug resistance. The findings demonstrated that c-FLIP stabilized FoxM1 by inhibiting its ubiquitination, and promoted the resistance of NSCLC cells to thiostrepton and osimertinib by upregulating FoxM1. The combination of FoxM1 and c-FLIP was found to be a more accurate prognostic biomarker for NSCLC patients.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Aimin Wang, Yue Shang, Jun Ni, Wendie Wang, Chen Wang, Gaojie Li, Shu-zhen Chen
Summary: The combination of ubenimex and celecoxib has shown significant anti-colorectal cancer effects in vitro and in vivo, with enhanced efficacy compared to single drug usage. The two drugs work together to induce stronger cell-cycle arrest and inhibit TK1 protein expression, making them a promising regimen for colorectal cancer treatment and providing potential for future drug development.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Jun Ni, Yue Shang, Wen-die Wang, Chen Wang, Ai-min Wang, Gao-jie Li, Shu-zhen Chen
Summary: Inhibiting FASN enhances bestatin-induced apoptosis in tumor cells through the up-regulation of PEPT1. This study reveals the correlation between FASN and PEPT1 in tumor cells and provides a new strategy for tumor targeted therapy.
CURRENT MOLECULAR PHARMACOLOGY
(2023)
Article
Immunology
Juan Zhang, Jincai Wang, Yue Shang, Yang Chen, Shuzhen Chen, Qiyang He
Summary: This study demonstrates for the first time that BON reduces PD-L1 protein level through the AMPK-mediated endoplasmic reticulum-associated degradation pathway, and it also exhibits synergism with gefitinib.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Letter
Medicine, General & Internal
Hana A. Mansour, Eugenie Bitar, Youssef Fares, Assad A. Makdessi, Antoine Maalouf, Mahmoud El Ghoul, Mohamad A. Mansour, Antoine Chami, Michel Khalil, Alex Jalkh, Daniel Cherfan, Jawad Fares, Fadlo R. Khuri, Ahmad M. Mansour
Article
Biochemistry & Molecular Biology
Fadlo R. Khuri
Summary: Higher education and healthcare sectors are facing challenges due to the COVID-19 pandemic. The Faculty of Medicine at the American University of Beirut is adapting to the situation and focusing on improving medical education to survive the crisis.
Article
Oncology
Jun Ni, Xiaofei Wang, Yue Shang, Yi Li, Shuzhen Chen
Summary: The study demonstrated that CD13 inhibition cooperates with TRAIL to enhance DR4-mediated cell death, increasing sensitivity of tumor cells to TRAIL-induced killing and promoting the expression and stabilization of DR4. CD13 inhibition has emerged as an effective strategy for TRAIL/ DR4-based therapy.
CANCER BIOLOGY & MEDICINE
(2021)