Arsenic nanoparticles trigger apoptosis via anoikis induction in OECM-1 cells

Alejandra A. Covarrubias,; Reyna-Jeldes, M.; Pedroso-Santana S.; Marín, Sabrina A.; Madero-Mendoza, C.; Demergasso, C. S.; Claudio Coddou

Keywords: apoptosis, anoikis, squamous cell carcinoma, arsenic nanoparticles, OECM-1Bit-1

Abstract

Arsenic compounds have been used as therapeutic alternatives for several diseases including cancer. In the following work, we obtained arsenic nanoparticles (AsNPs) produced by an anaerobic bacterium from the Salar de Ascot & aacute;n, in northern Chile, and evaluated their effects on the human oral squamous carcinoma cell line OECM-1. Resazurin reduction assays were carried out on these cells using 1-100 mu M of AsNPs, finding a concentration-dependent reduction in cell viability that was not observed for the non-tumoral gastric mucosa-derived cell line GES-1. To establish if these effects were associated with apoptosis induction, markers like Bcl2, Bax, and cleaved caspase 3 were analyzed via Western blot, executor caspases 3/7 via luminometry, and DNA fragmentation was analyzed by TUNEL assay, using 100 mu M cisplatin as a positive control. OECM-1 cells treated with AsNPs showed an induction of both extrinsic and intrinsic apoptotic pathways, which can be explained by a significant decrease in P-Akt/Akt and P-ERK/ERK relative protein ratios, and an increase in both PTEN and p53 mRNA levels and Bit-1 relative protein levels. These results suggest a prospective mechanism of action for AsNPs that involves a potential interaction with extracellular matrix (ECM) components that reduces cell attachment and subsequently triggers anoikis, an anchorage-dependent type of apoptosis.

Más información

Título de la Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volumen: 25
Editorial: MDPI
Fecha de publicación: 2024
Página de inicio: 6723
Idioma: English
Financiamiento/Sponsor: FONDEQUIP EQM140100; grant “Núcleo para el estudio del cáncer a nivel básico, aplicado y clínico”, VRIDT, UCN; Millennium Nucleus for the Study of Pain (MiNuSPain). Millennium Scientific Initiative NCN19_038 of the Ministry of Science, Technology, Knowled
DOI:

DOI10.3390/ijms25126723

Notas: ISI