دورية أكاديمية
أعرض في EDS

NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.

التفاصيل البيبلوغرافية
العنوان: NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.
المؤلفون: Daressy F; CNRS UMR9018, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France., Séguy L; Normandie Université, UniCaen, CERMN, F-14000 Caen, France., Favre L; Inserm U955, Université Paris-Est Créteil, F-94009 Créteil, France; AP-HP, CHU Henri Mondor, Département de Pathologie, F-94009 Créteil, France., Corvaisier S; Normandie Université, UniCaen, CERMN, F-14000 Caen, France., Apel C; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France., Groo AC; Normandie Université, UniCaen, CERMN, F-14000 Caen, France., Litaudon M; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France., Dumontet V; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France., Malzert-Fréon A; Normandie Université, UniCaen, CERMN, F-14000 Caen, France., Desrat S; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France., Roussi F; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France., Robert A; Inserm UMR1279, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France. Electronic address: aude.robert@gustaveroussy.fr., Wiels J; CNRS UMR9018, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France. Electronic address: joelle.wiels@gustaveroussy.fr.
المصدر: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Oct; Vol. 154, pp. 113546. Date of Electronic Publication: 2022 Aug 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE
أسماء مطبوعة: Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
مواضيع طبية MeSH: Antineoplastic Agents*/pharmacology , Hematologic Neoplasms*/drug therapy, Apoptosis ; Bridged Bicyclo Compounds, Heterocyclic ; Cell Line, Tumor ; Humans ; Leukocytes, Mononuclear/metabolism ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Myocytes, Cardiac/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Sulfonamides ; Winteraceae/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-X Protein/metabolism
مستخلص: The overexpression of antiapoptotic members (BCL-2, BCL-xL, MCL-1, etc.) of the BCL-2 family contributes to tumor development and resistance to chemotherapy or radiotherapy. Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax). However, acquired resistance to venetoclax or chemotherapy drugs due to an upregulation of MCL-1 has been observed, rendering MCL-1 an attractive new target for treatment. Six MCL-1 inhibitors (S64315, AZD-5991, AMG-176, AMG-397, ABBV-467 and PRT1419) have been evaluated in clinical trials since 2016, but some were affected by safety issues and none are currently used clinically. There is, therefore, still a need for alternative molecules. We previously described two drimane derivatives as the first covalent BH3 mimetics targeting MCL-1. Here, we described the characterization and biological efficacy of one of these compounds (NA1-115-7), isolated from Zygogynum pancheri, a plant belonging to the Winteraceae family. NA1-115-7 specifically induced the apoptosis of MCL-1-dependent tumor cells, with two hours of treatment sufficient to trigger cell death. The treatment of lymphoma cells with NA1-115-7 stabilized MCL-1, disrupted its interactions with BAK, and rapidly induced apoptosis through a BAK- and BAX-mediated process. Importantly, a similar treatment with NA1-115-7 was not toxic to erythrocytes, peripheral blood mononuclear cells, platelets, or cardiomyocytes. These results highlight the potential of natural products for use as specific BH3 mimetics non-toxic to normal cells, and they suggest that NA1-115-7 may be a promising tool for use in cancer treatment.
Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
فهرسة مساهمة: Keywords: B-cell lymphoproliferation; BAK; BAX; BH3-mimetics; Drimane sesquiterpenoids; MCL-1 inhibitor
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Bridged Bicyclo Compounds, Heterocyclic)
0 (Myeloid Cell Leukemia Sequence 1 Protein)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Sulfonamides)
0 (bcl-2 Homologous Antagonist-Killer Protein)
0 (bcl-X Protein)
N54AIC43PW (venetoclax)
تواريخ الأحداث: Date Created: 20220821 Date Completed: 20220915 Latest Revision: 20220915
رمز التحديث: 20221213
DOI: 10.1016/j.biopha.2022.113546
PMID: 35988426
قاعدة البيانات: MEDLINE
الوصف
تدمد:1950-6007
DOI:10.1016/j.biopha.2022.113546