Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer

Autor: Carmela Salvatore, Mauro Provinciali, Gaetano Fiorillo, Paolo Lombardi, Fiorenza Orlando, Cristina Geroni, Elisa Pierpaoli, Francesco Piacenza
Jazyk: angličtina
Rok vydání: 2021
Předmět:
senescence
Cell
Berberine Alkaloids
Administration
Oral
p16
migration
lcsh:Chemistry
chemistry.chemical_compound
Mice
Berberine
Cell Movement
berberine
Medicine
NAX014
Neoplasm Metastasis
lcsh:QH301-705.5
Spectroscopy
Molecular Structure
Alkaloid
Brief Report
lung metastases
General Medicine
VEGF
Computer Science Applications
Neoplasm Proteins
Tumor Burden
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Toxicity
Female
Genetically modified mouse
Senescence
Antineoplastic Agents
Mice
Transgenic
Catalysis
Inorganic Chemistry
breast cancer
Cell Line
Tumor
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
business.industry
Organic Chemistry
Mammary Neoplasms
Experimental
Cell Cycle Checkpoints
Genes
erbB-2
In vitro
Rats
chemistry
lcsh:Biology (General)
lcsh:QD1-999
HER-2
TNF-α
Cancer cell
Cancer research
Drug Screening Assays
Antitumor
business
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 2653, p 2653 (2021)
International Journal of Molecular Sciences
ISSN: 1661-6596
1422-0067
Popis: The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of the BBR-derived NAX014 compound was able to counteract HER-2 overexpressing mammary tumors onset and progression in transgenic mice. However, the IP administration was found to induce organ toxicity at doses higher than 2.5 mg/Kg. In this study, we evaluated the effect of intragastric (IG) administration of 20 mg/kg of NAX014 on both safety and anticancer efficacy in HER-2/neu transgenic mice. Furthermore, cancer cell dissemination and migration, tumor cell senescence and immunological changes were examined. Our results demonstrated that IG NAX014 administration delayed the onset of mammary tumors with no negative effects on health and survival. NAX014 reduced HER-2 overexpressing BC cells migration in vitro and the frequency of lung metastasis in HER-2/neu transgenic mice. A statistically significant increase of senescence-associated p16 expression was observed in tumors from NAX014-treated mice, and the induction of cell senescence was observed in HER-2 overexpressing BC cells after in vitro treatment with NAX014. Although NAX014 did not modulate the presence of tumor-infiltrating lymphocytes, the level of circulating TNF-α and VEGF was found to be reduced in NAX014-treated mice. The overall results address the NAX014 compound as potential tool for therapeutic strategies against HER-2 overexpressing breast cancer.
Databáze: OpenAIRE
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