Ring-Substituted 1-Hydroxynaphthalene-2-Carboxanilides Inhibit Proliferation and Trigger Mitochondria-Mediated Apoptosis.

Abstract

Ring-substituted 1-hydroxynaphthalene-2-carboxanilides were previously investigated for their antimycobacterial properties. In our study, we have shown their antiproliferative and cell death-inducing effects in cancer cell lines. Cell proliferation and viability were assessed by WST-1 assay and a dye exclusion test, respectively. Cell cycle distribution, phosphatidylserine externalization, levels of reactive oxygen or nitrogen species (RONS), mitochondrial membrane depolarization, and release of cytochrome c were estimated by flow cytometry. Levels of regulatory proteins were determined by Western blotting. Our data suggest that the ability to inhibit the proliferation of THP-1 or MCF-7 cells might be referred to meta- or para-substituted derivatives with electron-withdrawing groups -F, -Br, or -CF3 at anilide moiety. This effect was accompanied by accumulation of cells in G1 phase. Compound 10 also induced apoptosis in THP-1 cells in association with a loss of mitochondrial membrane potential and production of mitochondrial superoxide. Our study provides a new insight into the action of salicylanilide derivatives, hydroxynaphthalene carboxamides, in cancer cells. Thus, their structure merits further investigation as a model moiety of new small-molecule compounds with potential anticancer properties.

• Authors: Tereza Kauerová, Tomáš Goněc, Josef Jampílek, Susanne Hafner, Ann-Kathrin Gaiser, Tatiana Syrovets, Radek Fedr, Karel Souček, Peter Kollar
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 10 (May 12 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32408543 (Publication Type: Journal Article)

Chemical References

• Anilides
• Antineoplastic Agents
• Naphthols
• Reactive Oxygen Species
• Salicylanilides
• Superoxides
• salicylanilide

Topics

• Anilides (chemistry, pharmacology)
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Humans
• MCF-7 Cells
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Molecular Structure
• Naphthols (chemistry)
• Reactive Oxygen Species (metabolism)
• Salicylanilides (chemistry, pharmacology)
• Structure-Activity Relationship
• Superoxides (metabolism)
• THP-1 Cells