Benzoxazine Dimer Analogue Targets Integrin β3 in Lung Cancer Cells and Suppresses Anoikis Resistance and Migration.


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
May 2020
Historique:
received: 09 03 2020
revised: 18 03 2020
accepted: 19 03 2020
entrez: 6 5 2020
pubmed: 6 5 2020
medline: 19 5 2020
Statut: ppublish

Résumé

Certain integrins including integrin β3 facilitate movement and survival of metastatic cancer cells. We examined whether benzoxazine dimer analogue N,N-bis(5-ethyl-2-hydroxybenzyl) methylamine (HM) has anti-metastatic effects. Cell viability was examined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Wound healing and phalloidin-rhodamine assays were performed to evaluate the migration and filopodia formation, respectively. Anoikis resistance was studied by anchorage-independent growth assay. The expression of proteins regulating migration were examined by western blot. HM treatment significantly inhibited growth and survival of detached lung cancer cells as indicated by the reduced colony number and size of anchorage-independent growth analysis. HM inhibited cell migration and suppressed filopodia formation. Protein analysis indicated that the compound dramatically decreased integrin β3 and its related downstream proteins including active focal adhesion kinase (FAK) and active protein kinase B (AKT); however, integrin β1 and α5 were found to be unaltered. HM shows a potential in targeting integrin β3 and could be a good candidate for further developed as an anti-metastatic therapy.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
Certain integrins including integrin β3 facilitate movement and survival of metastatic cancer cells. We examined whether benzoxazine dimer analogue N,N-bis(5-ethyl-2-hydroxybenzyl) methylamine (HM) has anti-metastatic effects.
MATERIALS AND METHODS METHODS
Cell viability was examined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Wound healing and phalloidin-rhodamine assays were performed to evaluate the migration and filopodia formation, respectively. Anoikis resistance was studied by anchorage-independent growth assay. The expression of proteins regulating migration were examined by western blot.
RESULTS RESULTS
HM treatment significantly inhibited growth and survival of detached lung cancer cells as indicated by the reduced colony number and size of anchorage-independent growth analysis. HM inhibited cell migration and suppressed filopodia formation. Protein analysis indicated that the compound dramatically decreased integrin β3 and its related downstream proteins including active focal adhesion kinase (FAK) and active protein kinase B (AKT); however, integrin β1 and α5 were found to be unaltered.
CONCLUSION CONCLUSIONS
HM shows a potential in targeting integrin β3 and could be a good candidate for further developed as an anti-metastatic therapy.

Identifiants

pubmed: 32366403
pii: 40/5/2583
doi: 10.21873/anticanres.14229
doi:

Substances chimiques

Antineoplastic Agents 0
Benzoxazines 0
Integrin beta3 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2583-2589

Informations de copyright

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Nicharat Sriratanasak (N)

Department of Pharmacology and Physiology, and Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Nongyao Nonpanya (N)

Department of Pharmacology and Physiology, and Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Worawat Wattanathana (W)

Department of Materials Engineering, Faculty of Engineering, Kasetsart University, Bangkok, Thailand.

Pithi Chanvorachote (P)

Department of Pharmacology and Physiology, and Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand pithi.ch@gmail.com.

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Classifications MeSH