Article
Multidisciplinary Sciences
Chao Zhang, Xin Wang, Chuanbao Zhang
Summary: CDK2 was identified as the direct target of icaritin in tumor cells. Icaritin interacted with CDK2, resulting in downregulation of CDK2 activity and interference with complex formation. Additionally, icaritin modulated microRNA-597 expression, which reduced the stability and translation efficiency of CDK2-mRNA. In vitro and in vivo experiments demonstrated that icaritin inhibited proliferation and promoted apoptosis of tumor cells, similar to CDK2 inhibitor k03861.
Review
Biochemistry & Molecular Biology
Soni Savai Pullamsetti, Ravikumar Sitapara, Robin Osterhout, Astrid Weiss, Laura L. Carter, Lawrence S. Zisman, Ralph Theo Schermuly
Summary: Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and increased pulmonary vascular resistance. Histologically, PAH is characterized by plexiform and neointimal lesions composed of dysregulated endothelial cells and myofibroblasts. The PDGFR-CSF1R-c-KIT signaling network has been implicated in PAH pathogenesis, and inhibition of this network has potential therapeutic benefits. Seralutinib, which targets these pathways, shows promise for the treatment of PAH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Kun Zhang, Kaizhao Hu, Qian Li, Min Li, Ke Gao, Kecheng Yang, Bing Zhao, Xiao-Jing Shi, Lirong Zhang, Hong-Min Liu
Summary: Skp2 is a component of cullin-RING ligases, and its high expression is associated with aggressive tumor tissues and poor prognosis. In this study, a series of new Skp2 inhibitors were synthesized and their structure-activity relationship was systematically studied. Among them, compound 14i showed potent activity against Skp2 and exhibited effective anticancer effects on PC-3 and MGC-803 cells as well as xenograft mouse models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Inga-Marie Schaefer, Matthew L. Hemming, Meijun Z. Lundberg, Matthew P. Serrata, Isabel Goldaracena, Ninning Liu, Peng Yin, Joao A. Paulo, Steven P. Gygi, Suzanne George, Jeffrey A. Morgan, Monica M. Bertagnolli, Ewa T. Sicinska, Chen Chu, Shanshan Zheng, Adrian Marino-Enriquez, Jason L. Hornick, Chandrajit P. Raut, Wen-Bin Ou, George D. Demetri, Sinem K. Saka, Jonathan A. Fletcher
Summary: The study identifies recurrent genomic aberrations in cell cycle regulators causing co-activation of the CDK2 and CDK4/6 pathways in clinical GIST samples. Therapeutic co-targeting of CDK2 and CDK4/6 is synergistic in GIST cell lines with intact RB1, through inhibition of RB1 hyperphosphorylation and cell proliferation. RB1 inactivation and a novel oncogenic cyclin D1 resulting from an intragenic rearrangement (CCND1::chr11.g:70025223) are mechanisms of acquired CDK-inhibitor resistance in GIST.
BRITISH JOURNAL OF CANCER
(2022)
Review
Cell Biology
Dexin Shen, Lingao Ju, Fenfang Zhou, Mengxue Yu, Haoli Ma, Yi Zhang, Tongzu Liu, Yu Xiao, Xinghuan Wang, Kaiyu Qian
Summary: Melatonin, as a potential therapy for prostate cancer, has significant antioxidant and anticancer abilities. Studies have shown that melatonin can inhibit the development of prostate cancer through different pathways, and the synergistic use with other drugs may have better effects.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Biochemistry & Molecular Biology
Ji Wang, Zongyu Xiao, Peng Li, Chunwang Wu, Yan Li, Qing Wang, Yanming Chen, Honglong Zhou, Zhi Li, Zhaotao Wang, Qing Lan, Yezhong Wang
Summary: PRMT6, a type I arginine methyltransferase, asymmetrically di-methylates the arginine residues of both histones and non-histones. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results.
Article
Oncology
Arafat Siddiqui, Manuela Tumiati, Alia Joko, Jouko Sandholm, Pia Roering, Sofia Aakko, Reetta Vainionpaa, Katja Kaipio, Kaisa Huhtinen, Liisa Kauppi, Johanna Tuomela, Sakari Hietanen
Summary: The study suggests that targeting DNA repair pathways can increase sensitivity of treatment-resistant cancers to chemotherapy. Combination treatment shows potential effectiveness in HR-proficient cancers like high-grade serous ovarian cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pathology
Ken Sasai, Kouichi Tabu, Takashi Saito, Yukio Matsuba, Takaomi C. Saido, Shinya Tanaka
Summary: GLI1 is able to transform immortalized human astrocytes, while FOXM1 fails to induce malignant transformation. The downregulation of p27(KIP1) contributes to the malignant features of transformed astrocytes. Models using immortalized/transformed astrocytes are useful for identifying essential changes required for glioma formation.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Biochemistry & Molecular Biology
Trisiani Affandi, Angela M. Ohm, Dany Gaillard, Ami Haas, Mary E. Reyland
Summary: The study demonstrates that tyrosine kinase inhibitors (TKIs) provide radioprotection to salivary gland tissues by enhancing DNA repair mechanisms. TKIs increase the repair of DNA double-stranded breaks, regulate pathways involved in DNA repair, and prime cells for more efficient repair post-irradiation, suggesting a potential clinical application in head and neck cancer patients receiving radiation therapy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Mark Hives, Jana Jurecekova, Jan Kliment, Marian Grendar, Peter Kaplan, Robert Dusenka, Daniel Evin, Marta Vilckova, Klaudia Hives Holeckova, Monika Kmetova Sivonova
Summary: Genetic variants in genes involved in the G1/S transition (CDK2, CCNE1, and p27(KIP1)) did not have a significant impact on prostate cancer risk or the expression/activity of their corresponding proteins. However, high CCNE1 expression was significantly associated with a higher tumor grade in patients with prostate cancer.
CANCER GENOMICS & PROTEOMICS
(2022)
Review
Oncology
Diana Gulei, Rares Drula, Gabriel Ghiaur, Anca Dana Buzoianu, Yelena Kravtsova-Ivantsiv, Ciprian Tomuleasa, Aaron Ciechanover
Summary: The ubiquitin-proteasome system (UPS) is crucial for protein degradation, and its dysregulation is closely related to malignant pathologies. KPC1, an E3 ubiquitin ligase component, plays a key role in cancer by regulating p27 signaling and the NF-xB pathway. KPC1 maintains the ubiquitination of cytoplasmic p27, influencing cell-cycle progression, and also induces the ubiquitination of p105 to control NF-xB signaling. Therapeutic reinforcement of the KPC1-p50 axis shows promising tumor suppressor activity in multiple malignancies.
Article
Multidisciplinary Sciences
Pelin Ayaz, Agatha Lyczek, YiTing Paung, Victoria R. Mingione, Roxana E. Iacob, Parker W. de Waal, John R. Engen, Markus A. Seeliger, Yibing Shan, David E. Shaw
Summary: The authors used molecular dynamics simulations to study the binding process of Abl kinase with the cancer drug imatinib. The simulations revealed that imatinib induces a large conformational change of the protein and identified a region in Abl kinase that is structurally unstable during binding. Mutations in this region confer imatinib resistance by exacerbating structural instability.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jolien Beeken, Sofie Kessels, Jean-Michel Rigo, Yeranddy A. Alpizar, Laurent Nguyen, Bert Brone
Summary: p27(kip1) plays a role in regulating morphological complexity in microglia and affects phagocytic uptake of synaptosomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Cheng-Han Tsai, Chun-Yuan Chang, Bing-Ze Lin, Yu-Lou Wu, Meng-Hsiu Wu, Liang-Tin Lin, Wen-Chien Huang, Jonathan D. Holz, Tzong-Jen Sheu, Jhih-Shian Lee, Richard N. Kitsis, Pei-Han Tai, Yi-Jang Lee
Summary: The study found that cofilin-1 plays a crucial role in cell senescence by affecting morphological changes and cell enlargement. It induces cell senescence through the regulation of p27(Kip1), independent of p53 and p16(INK4) expressions. Additionally, cofilin-1 upregulation can also induce the expression of p27(Kip1) by suppressing the TEAD1 transcription factor, which in turn leads to senescence-related phenotypes.
Article
Biochemistry & Molecular Biology
Ignacio Colon-Mesa, Marta Fernandez-Galilea, Neira Sainz, Marta Lopez-Yus, Jose M. Artigas, Jose Miguel Arbones-Mainar, Elisa Felix-Soriano, Xavier Escote, Maria Jesus Moreno-Aliaga
Summary: Aging is often associated with increased fat accumulation and related comorbidities, with differences observed in the expression of p27 and cdk2 in different adipose tissue depots during aging and obesity. These findings suggest that p27 and cdk2 may contribute to metabolic differences in adipose tissue depots.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Stefano Sainas, Agnese C. Pippione, Marta Giorgis, Elisa Lupino, Parveen Goyal, Cristina Ramondetti, Barbara Buccinna, Marco Piccinini, Rodolpho C. Braga, Carolina H. Andrade, Mikael Andersson, Ann-Christin Moritzer, Rosmarie Friemann, Stefano Mensa, Salam Al-Kadaraghi, Donatella Boschi, Marco L. Lolli
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Agnese C. Pippione, Antonella Federico, Alex Ducime, Stefano Sainas, Donatella Boschi, Alessandro Barge, Elisa Lupino, Marco Piccinini, Michael Kubbutat, Jean-Marie Contreras, Christophe Morice, Salam Al-Karadaghi, Marco L. Lolli
Article
Chemistry, Medicinal
Stefano Sainas, Agnese C. Pippione, Elisa Lupino, Marta Giorgis, Paola Circosta, Valentina Gaidano, Parveen Goyal, Davide Bonanni, Barbara Rolando, Alessandro Cignetti, Alex Ducime, Mikael Andersson, Michael Jarva, Rosmarie Friemann, Marco Piccinini, Cristina Ramondetti, Barbara Buccinna, Salam Al-Karadaghi, Donatella Boschi, Giuseppe Saglio, Marco L. Lolli
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Agnese C. Pippione, Stefano Sainas, Antonella Federico, Elisa Lupino, Marco Piccinini, Michael Kubbutat, Jean-Marie Contreras, Christophe Morice, Alessandro Barge, Alex Ducime, Donatella Boschi, Salam Al-Karadaghi, Marco L. Lolli
Article
Biochemistry & Molecular Biology
Giovanni De Marco, Annarosa Lomartire, Giorgia Mandili, Elisa Lupino, Barbara Buccinna, Cristina Ramondetti, Cristina Moglia, Francesco Novelli, Marco Piccinini, Michael Mostert, Maria Teresa Rinaudo, Adriano Chio, Andrea Calvo
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2014)
Article
Chemistry, Medicinal
Clara Cena, Paolo Tosco, Elisabetta Marini, Loretta Lazzarato, Marco Piccinini, Cristina Ramondetti, Elisa Lupino, Roberta Fruttero, Alberto Gasco
Article
Immunology
Elisa Lupino, Cristina Ramondetti, Marco Piccinini
JOURNAL OF IMMUNOLOGY
(2012)
Correction
Chemistry, Medicinal
Stefano Sainas, Agnese C. Pippione, Elisa Lupino, Marta Giorgis, Paola Circosta, Valentina Gaidano, Parveen Goyal, Davide Bonanni, Barbara Rolando, Alessandro Cignetti, Alex Ducime, Mikael Andersson, Michael Jarva, Rosmarie Friemann, Marco Piccinini, Cristina Ramondetti, Barbara Buccinna, Salam Al-Karadaghi, Donatella Boschi, Giuseppe Saglio, Marco L. Lolli
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Stefano Sainas, Marta Giorgis, Paola Circosta, Valentina Gaidano, Davide Bonanni, Agnese C. Pippione, Renzo Bagnati, Alice Passoni, Yaqi Qiu, Carina Florina Cojocaru, Barbara Canepa, Alessandro Bona, Barbara Rolando, Mariia Mishina, Cristina Ramondetti, Barbara Buccinna, Marco Piccinini, Mohammad Houshmand, Alessandro Cignetti, Enrico Giraudo, Salam Al-Karadaghi, Donatella Boschi, Giuseppe Saglio, Marco L. Lolli
Summary: Compound 1 is a potent hDHODH inhibitor that induces AML cell differentiation and shows good metabolic stability and safety in mice. Compound 17, on the other hand, exhibits stronger activity in inducing AML cell differentiation, apoptosis, and lower cytotoxicity towards non-AML cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Barbara Buccinna, Cristina Ramondetti, Marco Piccinini
Summary: In this study, the effects of lapatinib alone and in combination with AMPK activator GSK-621 were evaluated in HER2-overexpressing breast cancer cells. The results show that the combination of these two drugs can reduce lapatinib-mediated HER3 upregulation and prevent reactivation of AKT and ERK1/2 kinases. The combination treatment synergistically decreases cell viability and greatly reduces the ability of NRG to rescue cell proliferation. Additionally, it hampers the establishment of a transcriptionally permissive chromatin structure at the HER3 promoter.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Stefano Sainas, Marta Giorgis, Paola Circosta, Giulio Poli, Marta Alberti, Alice Passoni, Valentina Gaidano, Agnese C. Pippione, Nicoletta Vitale, Davide Bonanni, Barbara Rolando, Alessandro Cignetti, Cristina Ramondetti, Alessia Lanno, Davide M. Ferraris, Barbara Canepa, Barbara Buccinna, Marco Piccinini, Menico Rizzi, Giuseppe Saglio, Salam Al-Karadaghi, Donatella Boschi, Riccardo Miggiano, Tiziano Tuccinardi, Marco L. Lolli
Summary: This study reports a compound 4 with dual activity as a human dihydroorotate dehydrogenase inhibitor and an anti-leukemic agent, which exhibits potent inhibition and pro-differentiating abilities in AML cells, low cytotoxicity on non-AML cells, and significant anti-leukemic activity in vivo in a xenograft mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)