Review
Biochemistry & Molecular Biology
Michael Latour, Nam-Gu Her, Santosh Kesari, Elmar Nurmemmedov
Summary: The WNT signaling pathway plays a crucial role in glioblastoma genesis and therapy resistance, presenting a therapeutic challenge. Current targeted therapies under clinical investigation may offer new treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Noha M. Abd El-Fadeal, Mohamed S. Nafie, Mohammed K. El-kherbetawy, Amr El-mistekawy, Hala M. F. Mohammad, Alaaeldeen M. Elbahaie, Abdullah A. Hashish, Suliman Y. Alomar, Sheka Yagub Aloyouni, Mohamed El-dosoky, Khaled M. Morsy, Sawsan A. Zaitone
Summary: This study demonstrates that nitazoxanide can induce cytotoxicity and promote apoptosis in colon cancer cells by inhibiting the Wnt/beta-catenin signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Lina Qi, Jiani Chen, Biting Zhou, Kailun Xu, Kailai Wang, Zhihao Fang, Yingkuan Shao, Ying Yuan, Shu Zheng, Wangxiong Hu
Summary: HOXC6 is overexpressed in right-sided colon cancer and promotes migration and invasion of colon cancer cells by activating the Wnt/beta-catenin signaling pathway. Silencing of HOXC6 can make colon cancer cells more sensitive to irinotecan.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Qihong Nie, Wei Wei Peng, Yuli Wang, Liting Zhong, Xuebing Zhang, Ling Zeng
Summary: This study revealed that berberine can inhibit the proliferation of colon cancer cells by regulating the β-catenin signaling pathway. The expression level of CTNNB1, the active component of berberine, was found to be higher in colon cancer patients compared to normal controls. This suggests that CTNNB1 may have potential clinical diagnostic and therapeutic value in colon cancer.
Article
Biochemistry & Molecular Biology
Mei-Jen Hsieh, Ching-Chieh Weng, Yu-Chun Lin, Chia-Chen Wu, Li-Tzong Chen, Kuang-Hung Cheng
Summary: This study revealed the importance of the Wnt/β-catenin signaling pathway in pancreatic cancer, showing that loss of LKB1 affects cystadenoma development and that the beta-catenin inhibitor FH535 can effectively suppress LKB1 loss-driven cystadenoma and slow down pancreatic cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Ayumi Kanemaru, Yuki Ito, Michiko Yamaoka, Yuki Shirakawa, Kou Yonemaru, Shunsuke Miyake, Misaki Ando, Masako Ota, Takeshi Masuda, Akitake Mukasa, Jian-Dong Li, Hideyuki Saito, Takuichiro Hide, Hirofumi Jono
Summary: The downregulation of tumor suppressor CYLD is associated with poor prognosis in GBM patients. The Wnt/β-catenin signaling pathway is significantly activated in CYLD-downregulated GBM patients. Inhibiting this pathway can suppress the malignant characteristics induced by CYLD downregulation in GBM.
Review
Oncology
Esther Martinez-Font, Marina Perez-Capo, Oliver Vogler, Javier Martin-Broto, Regina Alemany, Antonia Obrador-Hevia
Summary: Soft tissue sarcomas are a heterogeneous group of rare tumors originating from mesenchymal tissue, with chemotherapy based on doxorubicin remaining the standard first-line treatment. Understanding the molecular alterations of the WNT signaling pathway in STS is crucial for developing new therapeutic approaches and identifying drug targets.
Article
Biochemistry & Molecular Biology
Gabriela C. Somaini, Manuel J. Aybar, Nancy R. Vera, Celeste Tribulo
Summary: The study found that Geoffroea decorticans extracts can regulate embryonic development signaling pathway, reduce beta-catenin levels, inhibit cancer cell growth, and may have anticancer effects.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Jiong Ning, Qi Sun, Zijie Su, Lifeng Tan, Yun Tang, Sapna Sayed, Huan Li, Vivian Weiwen Xue, Shanshan Liu, Xianxiong Chen, Desheng Lu
Summary: CK1 delta/epsilon enhance beta-catenin-mediated transcription by regulating beta-catenin acetylation. CK1 delta/epsilon interact with Tip60 and facilitate its recruitment to the beta-catenin complex, leading to increased beta-catenin acetylation at K49. Furthermore, this study discovers that a complex consisting of CK1 delta/CK1 epsilon/beta-catenin/Tip60 is present in colon cancer cells, and this complex plays an important role in beta-catenin acetylation.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Cyrollah Disoma, Yuzheng Zhou, Shanni Li, Jian Peng, Zanxian Xia
Summary: The Wnt/β-catenin signaling pathway plays a crucial role in colorectal carcinogenesis, but no clinically approved therapies targeting this pathway currently exist. New modulators of the pathway are involved not only in cancer initiation but also in chemoresistance, epithelial-mesenchymal transition, and cancer stem cell renewal. CDX2 shows potential as a promising molecular target for colorectal cancer therapeutics, although further studies are needed to determine its significance. Overall, the regulation of the Wnt/β-catenin signaling pathway remains complex and not fully understood, posing a major barrier to the development of targeted chemotherapeutic agents.
Review
Biochemistry & Molecular Biology
Sarah Koushyar, Valerie S. Meniel, Toby J. Phesse, Helen B. Pearson
Summary: Aberrant activation of the Wnt pathway is closely related to tumor formation, progression, and therapeutic resistance in prostate cancer. Targeting the Wnt pathway for prostate cancer treatment has shown potential efficacy. However, the functional consequences of activating the Wnt pathway during different stages of prostate cancer progression are still unclear. Preclinical research on targeting Wnt signaling in the treatment of prostate cancer is crucial for identifying effective treatment strategies and improving patient care.
Article
Biochemistry & Molecular Biology
Young-Eun Cho, Jeong-Hee Kim, Young-Hyun Che, Yong-Jun Kim, Ji-Youn Sung, Yoon-Wha Kim, Bong-Geun Choe, Sun Lee, Jae-Hoon Park
Summary: ZKSCAN3 acts as an oncogenic transcription factor in human malignant tumors, and it has been identified as a downstream effector of the Wnt/β-catenin signaling pathway. It upregulates chromosomal instability in colon cancer cells by suppressing MAD2L2 expression. Moreover, the upregulation of ZKSCAN3 is an early event in the adenoma-carcinoma sequence during colon cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Yong Ji, Jian Lv, Di Sun, Yufeng Huang
Summary: This review explores the significant role of the Wnt/β-catenin signaling pathway in colorectal cancer tumorigenesis, metastasis, and recurrence, as well as its potential value in diagnosis and therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Endocrinology & Metabolism
Maria Cristina Carbajo-Garcia, Elena Juarez-Barber, Marina Segura-Benitez, Amparo Faus, Alexandra Trelis, Javier Monleon, Greta Carmona-Antonanzas, Antonio Pellicer, James M. Flanagan, Hortensia Ferrero
Summary: This study found that instability in H3K4me3 histone modification alters the expression of oncogenes and tumor suppressor genes, leading to malignant proliferation of uterine leiomyomas and dysregulated Wnt/beta-catenin and TGF-beta pathways. Reversal of these histone modifications may provide a promising new therapeutic approach for uterine leiomyoma patients.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2023)
Article
Anatomy & Morphology
Chunyi Ji, Lijian Chen, Miaoxian Yuan, Weixin Xie, Xinyi Sheng, Qiang Yin
Summary: This study investigates the mechanism of KDM1A-regulated hepatoblastoma (HB) development. The expression levels of KDM1A and DKK3 were analyzed in HB patients, and experiments were conducted on cell lines and nude mice to study the effects of knockdown of KDM1A and DKK3. The results suggest that KDM1A stimulates HB development by activating the Wnt/beta-catenin pathway through inhibition of DKK3 transcription.
Review
Biochemistry & Molecular Biology
Maurizio Bifulco, Erika Di Zazzo, Fabiana Napolitano, Anna Maria Malfitano, Giuseppe Portella
Summary: Since the nineteenth century, reports have shown that cancer patients occasionally experience clinical remission called Saint Peregrine tumor as a result of natural infections. The oncolytic activity of viruses, known as oncolytic viruses (OVs), which selectively infect and kill cancer cells, has been discovered. However, early attempts to increase OVs specificity, efficacy, and safety were inconclusive/negative, leading to a decline in research in this field. The renewal of interest in virotherapy occurred in the late 1990s with the development of genetic engineering techniques and a better understanding of cancer cells, resulting in the generation of potent and safe OVs.
Review
Chemistry, Multidisciplinary
Carole A. Bewley, Gary A. Sulikowski, Zhongyue J. Yang, Giuseppe Bifulco, Hyo-Moon Cho, Christopher R. Fullenkamp
Summary: Natural products, produced by enzymatic assembly lines, have played a crucial role in the discovery of antibiotics, antineoplastics, and therapeutics. They have unique three-dimensional shapes and stereochemistry, which determine their diverse functions and biological activities. With advancements in methods and tools, research on atropisomerism in natural products and related scaffolds is progressing.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Yves P. P. Auberson, Paola B. B. Arimondo, Maria Duca, Sebastian Essig, Uwe Grether, Arne C. C. Rufer, Gianluca Sbardella, Ulrich Schopfer, Antoni Torrens, Mario van Der Stelt, Boris Vauzeilles, Olalla Vazquez, Andrew D. X. Zhang
Summary: Ground-breaking research and method development in disease biology have led to the discovery of potential new drug targets. Chemical probes are increasingly being used in the drug discovery process, for target identification and assessment, as well as qualifying small molecules as drug candidates. The progress in probe chemistry has led to the development of novel assay formats and pharmaceutical compound classes. EFMC has launched the Chemical Biology Initiative to advance science in medicinal chemistry and chemical biology and represent the scientific community.
Review
Oncology
Cristina Pagano, Erika di Zazzo, Giorgio Avilia, Beatrice Savarese, Giovanna Navarra, Maria Chiara Proto, Donatella Fiore, Monica Rienzo, Patrizia Gazzerro, Chiara Laezza, Maurizio Bifulco
Summary: The epidemic spread of obesity is recognized as a global burden, and its link with cancer, known as adiponcosis, is of great interest in the scientific community. The mechanisms underlying adiponcosis, which may vary depending on cancer type, involve insulin resistance, chronic inflammation, and adipose tissue-derived hormones and cytokines. This review summarizes the current evidence on pathways, hormones, and interventions for obesity-related breast and colorectal cancers. It also discusses current targets and drugs for cancer treatment and potential therapeutic mechanisms.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Cristina Pagano, Beatrice Savarese, Laura Coppola, Giovanna Navarra, Giorgio Avilia, Chiara Laezza, Maurizio Bifulco
Summary: Cannabis sativa-derived compounds, such as THC and CBD, and components of the endocannabinoid system, such as AEA and 2-AG, have been extensively studied for their antioxidant effects. Many diseases are characterized by imbalanced ROS production, and these compounds have shown potential in reducing ROS levels in various pathological conditions. Further research on the antioxidant properties of cannabis sativa-derived compounds could have future clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Jean Quancard, Anna Vulpetti, Anders Bach, Brian Cox, Stephanie M. Gueret, Ingo V. Hartung, Hannes F. Koolman, Stefan Laufer, Josef Messinger, Gianluca Sbardella, Russell Craft
Summary: Hit generation is a crucial step in drug discovery that determines the speed and success rate of identifying drug candidates. Different strategies are available for identifying chemical starting points for each biological target. This article discusses the best practices for target-centric hit generation, validation of hits, and the design of integrated strategies to maximize the chance of identifying high-quality starting points.
Article
Biochemistry & Molecular Biology
Michela Pecoraro, Stefania Marzocco, Raffaella Belvedere, Antonello Petrella, Silvia Franceschelli, Ada Popolo
Summary: This study aimed to evaluate the protective effects of Simvastatin on Doxorubicin-induced cardiotoxicity. The results showed that Simvastatin co-treatment significantly reduced oxidative stress, calcium homeostasis disturbance, and apoptosis. Furthermore, Simvastatin co-treatment also affected the expression and cellular localization of Connexin 43, which is involved in cardioprotection. Based on these findings, Simvastatin could be a promising adjuvant in Doxorubicin anticancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michela Pecoraro, Adele Serra, Maria Pascale, Silvia Franceschelli
Summary: Correct protein folding is essential for cellular wellbeing, but accumulation of misfolded proteins in the endoplasmic reticulum (ER) can disrupt cellular homeostasis and cause ER stress. Protein misfolding has been implicated in various human diseases, including cancer, diabetes, and cystic fibrosis. The unfolded protein response (UPR) is activated in response to ER stress and involves the three ER-resident proteins, IRE1 alpha, PERK, and ATF6. This article highlights the importance of correct protein folding and the potential of the drug lumacaftor (Vx-809) in reducing ER stress and inflammation associated with protein misfolding. Rating: 8/10
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Francesco Fiorentino, Sara Sementilli, Martina Menna, Federica Turrisi, Stefano Tomassi, Francesca Romana Pellegrini, Angela Iuzzolino, Francesca D'Acunzo, Alessandra Feoli, Hannah Wapenaar, Sophie Taraglio, Caterina Fraschetti, Donatella Del Bufalo, Gianluca Sbardella, Frank J. Dekker, Alessandro Paiardini, Daniela Trisciuoglio, Antonello Mai, Dante Rotili
Summary: KAT8, a lysine acetyltransferase, is involved in the development and metastasis of various cancer types. Two newly developed compounds, 19 and 34, are selective KAT8 inhibitors with low-micromolar activity and show antiproliferative effects in cancer cell lines, while not affecting nontransformed cells. These compounds provide valuable tools for studying KAT8 biology and have potential for further optimization studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Federica Rogati, Chiara Maioli, Gianluigi Lauro, Diego Caprioglio, Daniela Imperio, Erika Del Grosso, Bruno Botta, Luisa Mannina, Giuseppe Bifulco, Cinzia Ingallina, Alberto Minassi
Summary: In this study, a vintage photochemical approach was used to discover an unexpected reactivity pathway related to Delta 1-3-oxo-pentacyclic triterpenic acids, leading to a new class of natural-unnatural 5(10 -> 1)abeo-pentacyclic triterpenic acids.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Medicinal
Alessandra Feoli, Giulia Iannelli, Alessandra Cipriano, Ciro Milite, Lei Shen, Zhihao Wang, Andrea Hadjikyriacou, Troy L. Lowe, Cyrus Safaeipour, Monica Viviano, Giuliana Sarno, Elva Morretta, Maria Chiara Monti, Yanzhong Yang, Steven G. Clarke, Sandro Cosconati, Sabrina Castellano, Gianluca Sbardella
Summary: PRMT7 and PRMT9 have been identified as important therapeutic targets, but their biological roles, functions, and structural requirements are still unclear. This study discovered a potent PRMT7/9 inhibitor and revealed its binding mode to the two enzymes. The inhibition of PRMT activity in cells was confirmed, and an effective AlphaLISA assay was developed for screening small molecule inhibitors of PRMT9.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Alessandra Cipriano, Monica Viviano, Alessandra Feoli, Ciro Milite, Giuliana Sarno, Sabrina Castellano, Gianluca Sbardella
Summary: NADPH oxidases (NOXs) are electron transporting membrane enzymes that generate reactive oxygen species (ROS). Selective NOX inhibitors have not yet been identified, making it challenging to use them as therapeutic targets in vivo. This Perspective provides an updated overview of small-molecule NOX inhibitors described in the last two decades, discussing their structures, activities, specificity, and the main biological assays used.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)