Article
Biochemistry & Molecular Biology
Sho Koyasu, Shoichiro Horita, Keisuke Saito, Minoru Kobayashi, Hiroshi Ishikita, Christalle C. T. Chow, Gouki Kambe, Shigeto Nishikawa, Toshi Menju, Akiyo Morinibu, Yasushi Okochi, Yoshiaki Tabuchi, Yasuhito Onodera, Norihiko Takeda, Hiroshi Date, Gregg L. Semenza, Ester M. Hammond, Hiroshi Harada
Summary: p53 deficiency triggers the activation of HIF-1 and ZBTB2 plays a crucial role in this process. ZBTB2 promotes invasion and growth of p53-deficient cancers and is associated with poor prognosis in lung cancer patients. ZBTB2 N-terminus-mimetic polypeptides inhibit ZBTB2 activity and suppress tumor aggressiveness.
Article
Food Science & Technology
Yan Xiong, Shiyao Xu, Beibei Fu, Wanyan Tang, Mohamed Y. Zaky, Rong Tian, Rui Yao, Shanfu Zhang, Qingting Zhao, Weiqi Nian, Xiaoyuan Lin, Haibo Wu
Summary: Vitamin C exerts an anticancer effect by modulating the competitive binding of HIF-1α and p53 to CBL, inhibiting cell proliferation and promoting cell apoptosis. The study provides a mechanistic rationale for the therapeutic use of VC in cancer treatment.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Gastroenterology & Hepatology
Yafei Zhang, Hongwei Lu, Hong Ji, Yiming Li
Summary: This study investigated the role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and p53 in mucosal apoptosis in portal hypertensive gastropathy (PHG). The results showed that HIF-1 alpha and p53 were significantly upregulated in the gastric mucosa of PHG patients and animal models, and inhibition of these molecules could attenuate apoptosis. It was also found that HIF-1 alpha regulated the p53-induced mucosal epithelial apoptotic signaling pathway. Therefore, HIF-1 alpha and p53 may be potential therapeutic targets for PHG.
DIGESTIVE AND LIVER DISEASE
(2023)
Review
Oncology
Nan Guo, Yan Chen, Yuhong Zhang, Yonghao Deng, Fancai Zeng, Xiang Li
Summary: Ferroptosis is a recently discovered type of programmed cell death characterized by the accumulation of iron-dependent lipid peroxidation. The mechanisms of ferroptosis may be related to lipid peroxidation accumulation, imbalance in amino acid antioxidant system, and disturbance of iron metabolism. APEX1 plays a crucial role in regulating intracellular redox balance and may serve as a potential inhibitor of ferroptotic cell death.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Xiao-Yan Gao, Ying-Yu Lai, Xue-Shan Luo, De-Wei Peng, Qiao-Qiao Li, Hui-Shan Zhou, Yu-Mei Xue, Hui-Ming Guo, Jun-Fei Zhao, Hui Yang, Su-Juan Kuang, Zhao-Yu Wang, Meng-Zhen Zhang, Chun-Yu Deng, Shu-Lin Wu, Fang Rao
Summary: This study investigates the potential role of acetyltransferase p300 in age-related atrial fibrosis. By analyzing microarray data from atrial tissue of AF patients and SR controls, the study finds a possible relationship between p300 and cellular senescence and fibrosis. Biochemical assays and in vivo electrophysiological examination further confirm the positive effects of p300 inhibitor and knockdown on improving atrial fibrosis, reducing senescence, and decreasing AF inducibility. These findings provide new insights into AF treatment, especially for the elderly.
Review
Cell Biology
Cen Zhang, Juan Liu, Jianming Wang, Tianliang Zhang, Dandan Xu, Wenwei Hu, Zhaohui Feng
Summary: Hypoxia is crucial in solid tumors, with HIF and p53 signaling pathways playing key roles in regulating cellular responses to hypoxia. The interplay between hypoxia and p53 pathways can impact cancer progression, with p53 regulating hypoxia and HIF signaling in various ways, while mutant p53 can promote cancer progression through interaction with hypoxia and HIF signaling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Toxicology
Menghao Zeng, Xuefeng Zhang, Wei Xing, Qianlu Wang, Guibin Liang, Zhihui He
Summary: This study revealed that tobacco smoke extract up-regulated USP7 and p300 to activate the p53 p21 pathway, leading to premature senescence of EPCs, which may be a molecular mechanism underlying COPD development.
TOXICOLOGY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Ping Hu, Linzhen Hu, Yizhan Chen, Fuqian Wang, Yang Xiao, Zhou Tong, Hua Li, Ming Xiang, Qingyi Tong, Yonghui Zhang
Summary: This study explored the anti-hepatocellular carcinoma (HCC) effects and mechanism of Chaetocochin J (CJ). CJ was found to inhibit proliferation, induce cell cycle arrest, disrupt metabolism, migration, and invasion, as well as induce caspase-dependent apoptosis in HepG2 and Hep3B cells. It was also shown to inhibit the activation of the PI3K/Akt/mTOR/p70S6K/4EBP1 pathway, suppress the expression of HIF-1 alpha, disrupt the binding of HIF-1 alpha/p300, and subsequently inhibit the expression of target genes.
BIOORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Mengdong Wang, Di Wang, Yue Lang, Anwen Shao, Rui Zhang, Jun Tang, Dongming Lai, Chenglu Xiao
Summary: HIF-1α is crucial for hypoxia response by upregulating gene expression. L3MBTL3, regulated by HIF-1α, interacts with and promotes the degradation of HIF-1α in the nucleus, forming a negative feedback loop to dampen the hypoxic response.
Article
Biochemistry & Molecular Biology
Jinhua Tang, Hongyan Deng, Zixuan Wang, Huangyuan Zha, Qian Liao, Chunchun Zhu, Xiaoyun Chen, Xueyi Sun, Shuke Jia, Gang Ouyang, Xing Liu, Wuhan Xiao
Summary: The lysine monomethylase SET7 catalyzes the methylation of EGLN1, inhibiting its enzymatic activity and promoting cellular adaptation to hypoxic conditions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Gabriela Antonio-Andres, Gustavo U. Martinez-Ruiz, Mario Morales-Martinez, Elva Jimenez-Hernandez, Estefany Martinez-Torres, Tania V. Lopez-Perez, Laura A. Estrada-Abreo, Genaro Patino-Lopez, Sergio Juarez-Mendez, Victor M. Davila-Borja, Sara Huerta-Yepez
Summary: This study reveals that HIF-1 alpha can transcriptionally regulate YY1, and the expression of HIF-1 alpha positively correlates with YY1 in leukemia patients, suggesting that they may serve as therapeutic targets or biomarkers for ALL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Nasim Kheshtchin, Jamshid Hadjati
Summary: Hypoxia, a common characteristic of solid tumors, contributes to different aspects of tumor progression and limits the efficacy of immunotherapies. Developing new immunotherapy strategies involving therapeutic targeting of HIF-1 molecules associated with hypoxia may enhance the clinical effectiveness of immunotherapy. Targeting hypoxia presents a potential opportunity to improve the clinical benefit of cancer immunotherapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dong Zhao, Shanliang Zheng, Xingwen Wang, Hao Liu, Kunming Zhao, Li Li, Ying Hu
Summary: In certain tumors, iASPP plays a crucial role in the activation of HIF-1α. Inhibition of iASPP can slow down tumor growth, reduce angiogenesis, increase tumor necrosis, and decrease glycolysis dependent on HIF-1α. Mechanistically, iASPP directly binds VHL and prevents its binding to HIF-1α, leading to the stabilization of HIF-1α.
Article
Biochemistry & Molecular Biology
Yong Zhang, Li Jiang, Nianqun Qin, Mi Cao, Xiujuan Liang, Rensheng Wang
Summary: This study reveals that under hypoxic conditions, hCINAP regulates the migration and EMT of cervical cancer cells through the Akt-mTOR signaling pathway, while also inhibiting hypoxia-induced p53-dependent apoptosis. This suggests that hCINAP may play essential roles in cervical cancer metastasis and could be a potential target for the treatment of cervical cancer.
BIOCHEMISTRY AND CELL BIOLOGY
(2021)
Article
Environmental Sciences
Xianping Huang, Weihe Zhou, Yuefeng Zhang
Summary: The research revealed that in a hypoxic microenvironment, YY1 interacts with HIF-1 alpha to regulate the stemness of lung cancer cells.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Lorenzo Botta, Silvia Filippi, Bruno Mattia Bizzarri, Roberta Meschini, Manuela Caputo, Luca Proietti-De-Santis, Concetta Iside, Angela Nebbioso, Giampiero Gualandi, Raffaele Saladino
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Oncology
Fatma Mehrez, Karim Bougatef, Elisa Delle Monache, Ivan Arisi, Luca Proietti-De-Santis, Giorgio Prantera, Lilia Zouiten, Manuela Caputo, Amel Ben Ammar Elgaaied, Silvia Bongiorni
Article
Chemistry, Multidisciplinary
Lorenzo Botta, Silvia Filippi, Bruno M. Bizzarri, Claudio Zippilli, Roberta Meschini, Rebecca Pogni, Maria Camilla Baratto, Luciano Villanova, Raffaele Saladino
Article
Chemistry, Medicinal
Lorenzo Botta, Silvia Filippi, Claudio Zippilli, Silvia Cesarini, Bruno Mattia Bizzarri, Angela Cirigliano, Teresa Rinaldi, Alessandro Paiardini, Diego Fiorucci, Raffaele Saladino, Rodolfo Negri, Pietro Benedetti
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Multidisciplinary Sciences
Elena Paccosi, Federico Costanzo, Michele Costantino, Alessio Balzerano, Laura Monteonofrio, Silvia Soddu, Giorgio Prantera, Stefano Brancorsini, Jean-Marc Egly, Luca Proietti-De-Santis
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Cell Biology
Elena Paccosi, Luca Proietti-De-Santis
Summary: The study aims to investigate the unified molecular function of CSA and CSB proteins in the cascade of events leading to ubiquitin/proteasome-directed protein degradation associated with Cockayne Syndrome, to potentially identify the ubiquitin-proteasome machinery as a new therapeutic target for comprehensive treatment.
MECHANISMS OF AGEING AND DEVELOPMENT
(2021)
Article
Chemistry, Medicinal
Lorenzo Botta, Silvia Cesarini, Claudio Zippilli, Silvia Filippi, Bruno Mattia Bizzarri, Maria Camilla Baratto, Rebecca Pogni, Raffaele Saladino
Summary: One of the dihydroartemisinin and artesunic acid dimers, bearing 4-hydroxybenzyl alcohol as a spacer, showed high antimelanoma activity and low cytotoxicity towards normal fibroblast cells. The occurrence of a radical mechanism was hypothesized by DFO and EPR analyses, highlighting the role of artesunic acid scaffold in controlling toxicity and antimelanoma activity.
Article
Biochemistry & Molecular Biology
Elena Paccosi, Michele Costantino, Alessio Balzerano, Silvia Filippi, Stefano Brancorsini, Luca Proietti-De-Santis
Summary: Neuroblastoma is a common solid tumor in early childhood, presenting challenges in treatment due to its genetic and clinical heterogeneity. High-risk cases have poor outcomes with high mortality rates despite intensive therapies. Suppression of CSB through RNAi has been shown to significantly impair the tumorigenicity of neuroblastoma cells, indicating potential as a new anticancer strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sofia Gabellone, Davide Piccinino, Silvia Filippi, Tiziana Castrignano, Claudio Zippilli, Davide Del Buono, Raffaele Saladino
Summary: In this study, novel thymine biomimetic photo-adducts with alkane spacers were synthesized and found to have antimelanoma activity against human Topoisomerase 1 (TOP1)-overexpressing cancer cell lines. Molecular docking analysis showed that Dewar Valence photo-adducts had the highest affinity towards TOP1/DNA complex. The antimelanoma activity of these photo-adducts was retained when loaded into UV photo-protective lignin nanoparticles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Samanta Mecocci, Daniele Pietrucci, Marco Milanesi, Luisa Pascucci, Silvia Filippi, Vittorio Rosato, Giovanni Chillemi, Stefano Capomaccio, Katia Cappelli
Summary: The study found that milk extracellular vesicles contain a large amount of RNA and have potential immune regulatory effects. Different species of mEVs share some important miRNAs and exhibit functional differences.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Ilaria D'Agostino, Claudia Ardino, Giulio Poli, Filomena Sannio, Massimiliano Lucidi, Federica Poggialini, Daniela Visaggio, Enrico Rango, Silvia Filippi, Elena Petricci, Paolo Visca, Lorenzo Botta, Jean-Denis Docquier, Elena Dreassi
Summary: The ever-faster rise of antimicrobial resistance poses a major challenge to global public health. Researchers have developed a novel class of broad-spectrum bactericidal agents called AlkylGuanidino Ureas (AGU) that likely target bacterial membranes. By synthesizing a library of AGU derivatives and conducting specific assays, they have provided evidence that AGUs disrupt bacterial membranes without hemolytic behavior.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Silvia Filippi, Elena Paccosi, Alessio Balzerano, Margherita Ferretti, Giulia Poli, Juri Taborri, Stefano Brancorsini, Luca Proietti-De-Santis
Summary: The increased expression of Cockayne Syndrome group A (CSA) protein in breast cancer cells provides a potential target for effective anti-cancer therapies. The suppression of CSA by ASOs has shown promising results in reducing tumorigenicity and increasing sensitivity to chemotherapy in breast cancer cells.
Review
Biochemistry & Molecular Biology
Elena Paccosi, Alessio Balzerano, Luca Proietti-De-Santis
Summary: The serine/threonine kinase Akt plays a crucial role in various cellular activities and is frequently dysregulated in human cancers. Targeting the ubiquitination processes that regulate Akt activation and inactivation shows promise for cancer therapy. This review discusses the functions and roles of Akt in human cancer, focusing on molecules and compounds that target the ubiquitin proteasome system and their implications for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)