دورية أكاديمية
أعرض في EDS

Therapeutic potential of LINS01 histamine H 3 receptor antagonists as antineoplastic agents for triple negative breast cancer.

التفاصيل البيبلوغرافية
العنوان: Therapeutic potential of LINS01 histamine H 3 receptor antagonists as antineoplastic agents for triple negative breast cancer.
المؤلفون: Ospital IA; Laboratorio de Biología Tumoral e Inflamación, Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1107, Argentina., Táquez Delgado MA; Laboratorio de Biología Tumoral e Inflamación, Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1107, Argentina., Nicoud MB; Laboratorio de Biología Tumoral e Inflamación, Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1107, Argentina., Corrêa MF; Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil., Borges Fernandes GA; Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil., Andrade IW; Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil., Lauretta P; Laboratorio de Biología Tumoral e Inflamación, Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1107, Argentina., Martínez Vivot R; Laboratorio de Biología Tumoral e Inflamación, Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1107, Argentina., Comba MB; Instituto de Investigaciones en Ingeniería Ambiental, Química y Biotecnología Aplicada (INGEBIO), Facultad de Química e Ingeniería del Rosario, Pontificia Universidad Católica Argentina (UCA), Rosario 2000, Argentina., Zanardi MM; Instituto de Investigaciones en Ingeniería Ambiental, Química y Biotecnología Aplicada (INGEBIO), Facultad de Química e Ingeniería del Rosario, Pontificia Universidad Católica Argentina (UCA), Rosario 2000, Argentina., Speisky D; Hospital Británico, Buenos Aires 1280, Argentina., Uriburu JL; Hospital Británico, Buenos Aires 1280, Argentina., Fernandes JPS; Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil., Medina VA; Laboratorio de Biología Tumoral e Inflamación, Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1107, Argentina. Electronic address: vanina_medina@uca.edu.ar.
المصدر: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 May; Vol. 174, pp. 116527. Date of Electronic Publication: 2024 Apr 04.
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 , Antineoplastic Agents*/therapeutic use , Histamine H3 Antagonists*/pharmacology , Histamine H3 Antagonists*/therapeutic use , Triple Negative Breast Neoplasms*/drug therapy , Triple Negative Breast Neoplasms*/pathology, Animals ; Female ; Humans ; Mice ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Mice, Inbred BALB C ; Receptors, Histamine H3/metabolism ; Receptors, Histamine H3/genetics ; Xenograft Model Antitumor Assays
مستخلص: The aims of this work were to evaluate the expression of histamine H 3 receptor (H 3 R) in triple negative breast cancer (TNBC) samples and to investigate the antitumoral efficacy and safety of the LINS01 series of H 3 R antagonists, through in silico, in vitro, and in vivo approaches. Antitumor activity of LINS01009, LINS01010, LINS01022, LINS01023 was assayed in vitro in 4T1 and MDA-MB-231 TNBC cells (0.01-100 μM), and in vivo in 4T1 tumors orthotopically established in BALB/c mice (1 or 20 mg/kg). Additionally, H 3 R expression was assessed in 50 human TNBC samples. We have described a higher H 3 R mRNA expression in basal-like/TNBC tumors vs. matched normal tissue using TCGA Pan-Cancer Atlas data, and a higher H 3 R expression in human tumor samples vs. peritumoral tissue evidenced by immunohistochemistry associated with poorer survival. Furthermore, while all the essayed compounds showed antitumoral properties, LINS01022 and LINS01023 exhibited the most potent antiproliferative effects by: i) inducing cell apoptosis and suppressing cell migration in 4T1 and MDA-MB-231 TNBC cells, and ii) inhibiting cell growth in paclitaxel-resistant 4T1 cells (potentiating the paclitaxel antiproliferative effect). Moreover, 20 mg/kg LINS01022 reduced tumor size in 4T1 tumor-bearing mice, exhibiting a safe toxicological profile and potential for druggability estimated by ADME calculations. We conclude that the H 3 R is involved in the regulation of TNBC progression, offering promising therapeutic potential for the novel LINS01 series of H 3 R antagonists.
Competing Interests: Declaration of Competing Interest All authors declare no potential competing interests.
(Copyright © 2024. Published by Elsevier Masson SAS.)
فهرسة مساهمة: Keywords: ADMET; Breast cancer; Cell proliferation; Histamine H(3) receptor; Methyl piperazines; Target therapy
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Histamine H3 Antagonists)
0 (Receptors, Histamine H3)
تواريخ الأحداث: Date Created: 20240405 Date Completed: 20240430 Latest Revision: 20240510
رمز التحديث: 20240511
DOI: 10.1016/j.biopha.2024.116527
PMID: 38579399
قاعدة البيانات: MEDLINE
الوصف
تدمد:1950-6007
DOI:10.1016/j.biopha.2024.116527