Differential effects of N-TiO2 nanoparticle and its photo-activated form on autophagy and necroptosis in human melanoma A375 cells.

Abstract:

:The manipulation of autophagy provides a new opportunity for highly effective anticancer therapies. Recently, we showed that photodynamic therapy (PDT) with nitrogen-doped titanium dioxide (N-TiO2 ) nanoparticles (NPs) could promote the reactive oxygen species (ROS)-dependent autophagy in leukemia cells. However, the differential autophagic effects of N-TiO2 NPs in the dark and light conditions and the potential of N-TiO2- based PDT for the treatment of melanoma cells remain unknown. Here we show that depending on the visible-light condition, the autophagic response of human melanoma A375 cells to N-TiO2 NPs switches between two different statuses (ie., flux or blockade) with the opposite outcomes (ie., survival or death). Mechanistically, low doses of N-TiO2 NPs (1-100 µg/ml) stimulate a nontoxic autophagy flux response in A375 cells, whereas their photo-activation leads to the impairment of the autophagosome-lysosome fusion, the blockade of autophagy flux and consequently the induction of RIPK1-mediated necroptosis via ROS production. These results confirm that photo-controllable autophagic effects of N-TiO2 NPs can be utilized for the treatment of cancer, particularly melanoma.

journal_name

J Cell Physiol

authors

Mohammadalipour Z,Rahmati M,Khataee A,Moosavi MA

doi

10.1002/jcp.29479

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

8246-8259

issue

11

eissn

0021-9541

issn

1097-4652

journal_volume

235

pub_type

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