Carbon-coated
iron oxide NPs (Fe3O4@aC) promote
cytotoxic effects in drug-induced senescent breast cancer cells with
different gene mutation statuses (left) that is mechanistically achieved
by the induction of reductive stress (decreased ROS production, elevated
levels of antioxidant proteins such as FOXO3a, SOD1, and GPX4) (right).
Reductive stress-mediated cytotoxicity (right) was accompanied by
inflammatory response (NFκB activation, increased secretion
of IL-6 and IL-8), nucleolar stress (relocation of nucleolar proteins),
increased levels of cell cycle inhibitors, and autophagy induction
(increased levels of BECN1 and LC3B) that, in turn, led to apoptotic
cell death as judged by phosphatidylserine (PS) externalization and
caspase 9 (mitochondrial pathway of apoptosis) and caspase 3 activation.
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