Arsenic Nanoparticles Trigger Apoptosis via Anoikis Induction in OECM-1 Cells
Resumen
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 Ascotán, 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 μM 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 μM 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.
