المؤلفون: Casertano, Marcello, Genovese, Massimo, Santi, Alice, Pranzini, Erica, Balestri, Francesco, Avunduk, Sibel

المساهمون: MÜ, Sağlık Hizmetleri Meslek Yüksekokulu (Marmaris), Tıbbi Hizmetler Ve Teknikler Bölümü, orcid:0000-0002-3644-1516, Avunduk, Sibel

مصطلحات موضوعية: Marine natural products, Dysidea avara, avarone, Sesquiterpene‑type quinones

الوصف: Type 2 diabetes mellitus (T2DM) is a complex disease characterized by impaired glucose homeostasis and serious long-term complications. First-line therapeutic options for T2DM treatment are monodrug therapies, often replaced by multidrug therapies to ensure that non-responding patients maintain target glycemia levels. The use of multitarget drugs instead of mono- or multidrug therapies has been emerging as a main strategy to treat multifactorial diseases, including T2DM. Therefore, modern drug discovery in its early stages aims to identify potential modulators for multiple targets; for this purpose, exploration of the chemical space of natural products represents a powerful tool. Our study demonstrates that avarone, a sesquiterpene quinone obtained from the sponge Dysidea avara, is capable of inhibiting in vitro PTP1B, the main negative regulator of the insulin receptor, while it improves insulin sensitivity, and mitochondria activity in C2C12 cells. We observe that when avarone is administered alone, it acts as an insulin-mimetic agent. In addition, we show that avarone acts as a tight binding inhibitor of aldose reductase (AKR1B1), the enzyme involved in the development of diabetic complications. Overall, avarone could be proposed as a novel natural hit to be developed as a multitarget drug for diabetes and its pathological complications.

وصف الملف: application/pdf

العلاقة: PHARMACEUTICS; Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; Casertano, M.; Genovese, M.; Santi, A.; Pranzini, E.; Balestri, F.; Piazza, L.; Del Corso, A.; Avunduk, S.; Imperatore, C.; Menna, M.; Paoli, P. Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara. Pharmaceutics 2023, 15, 528. https://doi.org/10.3390/pharmaceutics15020528Test; https://doi.org/10.3390/pharmaceutics15020528Test; https://hdl.handle.net/20.500.12809/10619Test; 15

الإتاحة: https://doi.org/20.500.12809/10619Test
https://doi.org/10.3390/pharmaceutics15020528Test
https://hdl.handle.net/20.500.12809/10619Test

المؤلفون: Bello, Claudia, Pranzini, Erica, Piemontese, Emanuele, Schrems, Maximilian, Taddei, Maria Letizia, Giovannelli, Lisa, Schubert, Mario, Becker, Christian F. W., Rovero, Paolo, Papini, Anna Maria

المصدر: ChemBioChem ; volume 24, issue 12 ; ISSN 1439-4227 1439-7633

الوصف: Post‐translational modifications affect protein biology under physiological and pathological conditions. Efficient methods for the preparation of peptides and proteins carrying defined, homogeneous modifications are fundamental tools for investigating these functions. In the case of mucin 1 (MUC1), an altered glycosylation pattern is observed in carcinogenesis. To better understand the role of MUC1 glycosylation in the interactions and adhesion of cancer cells, we prepared a panel of homogeneously O‐glycosylated MUC1 peptides by using a quantitative chemoenzymatic approach. Cell‐adhesion experiments with MCF‐7 cancer cells on surfaces carrying up to six differently glycosylated MUC1 peptides demonstrated that different glycans have a significant impact on adhesion. This finding suggests a distinct role for MUC1 glycosylation patterns in cancer cell migration and/or invasion. To decipher the molecular mechanism for the observed adhesion, we investigated the conformation of the glycosylated MUC1 peptides by NMR spectroscopy. These experiments revealed only minor differences in peptide structure, therefore clearly relating the adhesion behaviour to the type and number of glycans linked to MUC1.

الإتاحة: https://doi.org/10.1002/cbic.202200741Test

المؤلفون: Nesi, Ilaria, Della Bella, Chiara, Taddei, Maria Letizia, Santi, Alice, Pranzini, Erica, Paoli, Paolo, D’Elios, Mario Milco, Ramazzotti, Matteo, Genovese, Massimo, Caselli, Anna, Cirri, Paolo

المصدر: Frontiers in Oncology ; volume 13 ; ISSN 2234-943X

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: In the early stages of carcinogenesis, the transformed cells become “invisible” to the immune system. From this moment on, the evolution of the tumor depends essentially on the genotype of the primitive cancer cells and their subsequent genetic drift. The role of the immune system in blocking tumor progression from the earliest stages is largely underestimated because by the time tumors are clinically detectable, the immune system has already completely failed its task. Therefore, a clinical treatment capable of restoring the natural anti-tumor role of the immune system could prove to be the “ultimate weapon” against cancer. Herein, we propose a novel therapeutic approach for the treatment of solid cancer that exploits the capability of activated monocytes to transfer major histocompatibility complex I (MHC-I) molecules bound to antigenic peptides to cancer cells using microvesicles as cargo, making tumor cells target of a “natural” CD8 + T lymphocyte cytotoxic response.

الإتاحة: https://doi.org/10.3389/fonc.2023.1245248Test

المؤلفون: Mancini, Caterina, Lori, Giulia, Pranzini, Erica, Taddei, Maria Letizia

المصدر: Trends in Endocrinology & Metabolism ; volume 35, issue 3, page 263-276 ; ISSN 1043-2760

مصطلحات موضوعية: Endocrinology, Endocrinology, Diabetes and Metabolism

الإتاحة: https://doi.org/10.1016/j.tem.2023.11.005Test
https://api.elsevier.com/content/article/PII:S1043276023002448?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1043276023002448?httpAccept=text/plainTest

المؤلفون: De Miranda Capeloa, Tania Isabel, Krzystyniak, Joanna, Canas Rodriguez, Amanda, Payen, Valery L, Zampieri, Luca, Pranzini, Erica, Derouane, Françoise, Vazeille, Thibaut, Bouzin, Caroline, Duhoux, Francois, Murphy, Michael P., Porporato, Paolo E, Sonveaux, Pierre

المساهمون: UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - SSS/IREC/2IP - IREC Imaging Platform (2IP)

المصدر: Cancers, Vol. 14, no. 6, p. 1488 [1-13] (2022)

الوصف: In oncology, the occurrence of distant metastases often marks the transition from curative to palliative care. Such outcome is highly predictable for breast cancer patients, even if tumors are detected early, and there is no specific treatment to prevent metastasis. Previous observations indicated that cancer cell mitochondria are bioenergetic sensors of the tumor microenvironment that produce superoxide to promote evasion. Here, we tested whether mitochondria-targeted antioxidant MitoQ is capable to prevent metastasis in the MDA-MB-231 model of triple-negative human breast cancer in mice and in the MMTV-PyMT model of spontaneously metastatic mouse breast cancer. At clinically relevant doses, we report that MitoQ not only prevented metastatic take and dissemination, but also local recurrence after surgery. We further provide in vitro evidence that MitoQ does not interfere with conventional chemotherapies used to treat breast cancer patients. Since MitoQ already successfully passed Phase I safety clinical trials, our preclinical data collectively provide a strong incentive to test this drug for the prevention of cancer dissemination and relapse in clinical trials with breast cancer patients.

العلاقة: boreal:259446; http://hdl.handle.net/2078.1/259446Test; info:pmid/; urn:EISSN:2072-6694

الإتاحة: https://doi.org/10.3390/cancers14061488Test
http://hdl.handle.net/2078.1/259446Test

المؤلفون: De Miranda Capeloa, Tania Isabel, Krzystyniak, Joanna, d'Hose, Donatienne, canas Rodriguez, Amanda, Payen, Valery L, Zampieri, Luca, Van de Velde, Justine, Benyahia, Zohra, Pranzini, Erica, Vazeille, Thibaut, Fransolet, Maude, Bouzin, Caroline, Brusa, Davide, Michiels, Carine, Gallez, Bernard, Murphy, Michael P, Porporato, Paolo E, Sonveaux, Pierre

المساهمون: UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, UNamur - SBIO_URBC (unité de recherche en biologie cellulaire), UCL - SSS/IREC/2IP - IREC Imaging Platform (2IP)

المصدر: Cancers, Vol. 14, no. 6, p. 1516 [1-20] (2022)

الوصف: To successfully generate distant metastases, metastatic progenitor cells must simultaneously possess mesenchymal characteristics, resist to anoïkis, migrate and invade directionally, resist to redox and shear stresses in the systemic circulation, and possess stem cell characteristics. These cells primarily originate from metabolically hostile areas of the primary tumor, where oxygen and nutrient deprivation, together with metabolic waste accumulation, exert a strong selection pressure promoting evasion. Here, we followed the hypothesis according to which metastasis as a whole implies the existence of metabolic sensors. Among others, mitochondria are singled out as a major source of superoxide that supports the metastatic phenotype. Molecularly, stressed cancer cells increase mitochondrial superoxide production, which activates the transforming growth factor-β pathway through src directly within mitochondria, ultimately activating focal adhesion kinase Pyk2. The existence of mitochondria-targeted antioxidants constitutes an opportunity to interfere with the metastatic process. Here, using aggressive triple-negative and HER2-positive human breast cancer cell lines as models, we report that MitoQ inhibits all the metastatic traits that we tested in vitro. Compared to other mitochondria-targeted antioxidants, MitoQ already successfully passed Phase I safety clinical trials, which provides an important incentive for future preclinical and clinical evaluations of this drug for the prevention of breast cancer metastasis.

العلاقة: boreal:259445; http://hdl.handle.net/2078/259445Test; info:pmid/; urn:EISSN:2072-6694

الإتاحة: https://doi.org/10.3390/cancers14061516Test
http://hdl.handle.net/2078/259445Test

المؤلفون: Capeloa, Tania, Krzystyniak, Joanna, D’hose, Donatienne, Rodriguez, Amanda Canas, Payen, Valery L., Zampieri, Luca X., Van de Velde, Justine A., Benyahia, Zohra, Pranzini, Erica, Vazeille, Thibaut, Fransolet, Maude, Bouzin, Caroline, Brusa, Davide, Michiels, Carine, Gallez, Bernard, Murphy, Michael P., Porporato, Paolo E., Sonveaux, Pierre

المصدر: Capeloa , T , Krzystyniak , J , D’hose , D , Rodriguez , A C , Payen , V L , Zampieri , L X , Van de Velde , J A , Benyahia , Z , Pranzini , E , Vazeille , T , Fransolet , M , Bouzin , C , Brusa , D , Michiels , C , Gallez , B , Murphy , M P , Porporato , P E & Sonveaux , P 2022 , ' MitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity ' , Cancers , vol. 14 , ....

مصطلحات موضوعية: Breast cancer, Clonogenicity, Invasion, Metastasis, Migration, Mitochondria, Mitochondria-targeted antioxidant, Mitochondrial superoxide, MitoQ, Spheroids

الوصف: To successfully generate distant metastases, metastatic progenitor cells must simultaneously possess mesenchymal characteristics, resist to anoïkis, migrate and invade directionally, resist to redox and shear stresses in the systemic circulation, and possess stem cell characteristics. These cells primarily originate from metabolically hostile areas of the primary tumor, where oxygen and nutrient deprivation, together with metabolic waste accumulation, exert a strong selection pressure promoting evasion. Here, we followed the hypothesis according to which metastasis as a whole implies the existence of metabolic sensors. Among others, mitochondria are singled out as a major source of superoxide that supports the metastatic phenotype. Molecularly, stressed cancer cells increase mitochondrial superoxide production, which activates the transforming growth factor-β pathway through src directly within mitochondria, ultimately activating focal adhesion kinase Pyk2. The existence of mitochondria-targeted antioxidants constitutes an opportunity to interfere with the metastatic process. Here, using aggressive triple-negative and HER2-positive human breast cancer cell lines as models, we report that MitoQ inhibits all the metastatic traits that we tested in vitro. Compared to other mitochondria-targeted antioxidants, MitoQ already successfully passed Phase I safety clinical trials, which provides an important incentive for future preclinical and clinical evaluations of this drug for the prevention of breast cancer metastasis.

وصف الملف: application/pdf

العلاقة: https://researchportal.unamur.be/en/publications/79568146-2b03-4709-9970-3c3b46f4a790Test

الإتاحة: https://doi.org/10.3390/cancers14061516Test
https://researchportal.unamur.be/en/publications/79568146-2b03-4709-9970-3c3b46f4a790Test
https://pure.unamur.be/ws/files/63098635/127_Capeloa_MitoQ_breast_Cancer_1_full.pdfTest
http://www.scopus.com/inward/record.url?scp=85126556232&partnerID=8YFLogxKTest

المؤلفون: Pranzini, Erica, Pardella, Elisa, Muccillo, Livio, Leo, Angela, Nesi, Ilaria, Santi, Alice, Parri, Matteo, Zhang, Tong, Huerta Uribe, Alejandro, Lottini, Tiziano, Sabatino, Lina, Caselli, Anna, Arcangeli, Annarosa, Raugei, Giovanni, Colantuoni, Vittorio, Cirri, Paolo, Chiarugi, Paola, Maddocks, Oliver D. K., Paoli, Paolo, Taddei, Maria Letizia

الوصف: 5-Fluorouracil (5-FU) is a key component of chemotherapy for colorectal cancer (CRC). 5-FU efficacy is established by intracellular levels of folate cofactors and DNA damage repair strategies. However, drug resistance still represents a major challenge. Here, we report that alterations in serine metabolism affect 5-FU sensitivity in in vitro and in vivo CRC models. In particular, 5-FU-resistant CRC cells display a strong serine dependency achieved either by upregulating endogenous serine synthesis or increasing exogenous serine uptake. Importantly, regardless of the serine feeder strategy, serine hydroxymethyltransferase-2 (SHMT2)-driven compartmentalization of one-carbon metabolism inside the mitochondria represents a specific adaptation of resistant cells to support purine biosynthesis and potentiate DNA damage response. Interfering with serine availability or affecting its mitochondrial metabolism revert 5-FU resistance. These data disclose a relevant mechanism of mitochondrial serine use supporting 5-FU resistance in CRC and provide perspectives for therapeutic approaches.

وصف الملف: text

العلاقة: https://eprints.gla.ac.uk/278241/1/278241.pdfTest; Pranzini, E. et al. (2022) SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis. Cell Reports , 40(7), 111233. (doi:10.1016/j.celrep.2022.111233 ) (PMID:35977477)

الإتاحة: https://doi.org/10.1016/j.celrep.2022.111233Test
https://eprints.gla.ac.uk/278241Test/
https://eprints.gla.ac.uk/278241/1/278241.pdfTest

المؤلفون: Raggi, Chiara, Taddei, Maria Letizia, Sacco, Elena, Navari, Nadia, Correnti, Margherita, Piombanti, Benedetta, Pastore, Mirella, Campani, Claudia, Pranzini, Erica, Iorio, Jessica, Lori, Giulia, Lottini, Tiziano, Peano, Clelia, Cibella, Javier, Lewinska, Monika, Andersen, Jesper B, di Tommaso, Luca, Vigano, Luca, Di Maira, Giovanni, Madiai, Stefania, Ramazzotti, Matteo, Orlandi, Ivan, Arcangeli, Annarosa, Chiarugi, Paola, Marra, Fabio

المساهمون: C. Raggi, M.L. Taddei, E. Sacco, N. Navari, M. Correnti, B. Piombanti, M. Pastore, C. Campani, E. Pranzini, J. Iorio, G. Lori, T. Lottini, C. Peano, J. Cibella, M. Lewinska, J.B. Andersen, L. di Tommaso, L. Vigano, G. Di Maira, S. Madiai, M. Ramazzotti, I. Orlandi, A. Arcangeli, P. Chiarugi, F. Marra

مصطلحات موضوعية: CCLP1, HUCCT1, OXPHOS, PGC-1α, SR-18292, Settore BIO/11 - Biologia Molecolare, Settore MED/04 - Patologia Generale

الوصف: BACKGROUND AND AIMS: Little is known about the metabolic regulation of cancer stem cells (CSC) in cholangiocarcinoma (CCA). We analyzed whether mitochondrial-dependent metabolism and related signaling pathways contribute to stem state in CCA.METHODS: The stem-like subset was enriched by sphere culture (SPH) in human intrahepatic CCA cells (HUCCT1 and CCLP1) and compared to cells cultured in monolayer. Extracellular flux analysis was examined by Seahorse technology and high-resolution respirometry. In patients with CCA, expression of factors related to mitochondrial metabolism was analyzed for possible correlation with clinical parameters.RESULTS: Metabolic analyses revealed a more efficient respiratory phenotype in CCA-SPH than in monolayers, due to mitochondrial oxidative phosphorylation. CCA-SPH showed high mitochondrial membrane potential and elevated mitochondrial mass, and over-expressed peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha, a master regulator of mitochondrial biogenesis. Targeting mitochondrial complex I in CCA-SPH by metformin, or PGC-1alpha silencing or pharmacologic inhibition (SR-18292) impaired spherogenicity and expression of markers related to the CSC phenotype, pluripotency, and epithelial-mesenchymal transition. In mice with tumor xenografts generated by injection of CCA-SPH, administration of metformin or SR-18292 significantly reduced tumor growth and determined a phenotype more similar to tumors originated from cells grown in monolayer. In CCA patients, expression of PGC-1alpha was correlated to expression of mitochondrial complex II and of stem-like genes. Patients with higher PGC-1alpha expression by immunostaining had lower overall survival (OS) and progression-free survival, higher angioinvasion and faster recurrence. In GSEA analysis, CCA patients with high levels of mitochondrial Complex II had shorter OS and time to recurrence.CONCLUSIONS: The CCA stem-subset has a more efficient respiratory phenotype and depends on mitochondrial oxidative metabolism ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33484774; info:eu-repo/semantics/altIdentifier/wos/WOS:000514835500084; numberofpages:14; journal:JOURNAL OF HEPATOLOGY; http://hdl.handle.net/2434/825203Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85104152123

الإتاحة: https://doi.org/10.1016/j.jhep.2020.12.031Test
http://hdl.handle.net/2434/825203Test

المؤلفون: Rinaldi, Gianmarco, Pranzini, Erica, Van Elsen, Joke, Broekaert, Dorien, Funk, Cornelius M., Planque, Mélanie, Doglioni, Ginevra, Altea-Manzano, Patricia, Rossi, Matteo, Geldhof, Vincent, Teoh, Shao Thing, Ross, Christina, Hunter, Kent W., Lunt, Sophia Y., Grünewald, Thomas G.P., Fendt, Sarah-Maria

المساهمون: KU Leuven, Stichting Tegen Kanker, Fonds Baillet Latour, Fonds Wetenschappelijk Onderzoek, European Research Council, Kom op tegen Kanker, Deutsche Krebshilfe

المصدر: Molecular Cell ; volume 81, issue 2, page 386-397.e7 ; ISSN 1097-2765

الإتاحة: https://doi.org/10.1016/j.molcel.2020.11.027Test
https://api.elsevier.com/content/article/PII:S1097276520308273?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1097276520308273?httpAccept=text/plainTest