2015
DOI: 10.18632/oncotarget.6233
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Novel p53-dependent anticancer strategy by targeting iron signaling and BNIP3L-induced mitophagy

Abstract: This study identifies BNIP3L as the key regulator of p53-dependent cell death mechanism in colon cancer cells targeted by the novel gallium based anticancer drug, KP46. KP46 specifically accumulated into mitochondria where it caused p53-dependent morphological and functional damage impairing mitochondrial dynamics and bioenergetics. Furthermore, competing with iron for cellular uptake, KP46 lowered the intracellular labile iron pools and intracellular heme. Accordingly, p53 accumulated in the nucleus where it … Show more

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Cited by 27 publications
(20 citation statements)
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“…However, in 2016, Wilfinger et al demonstrated that KP-46 caused caspase-3 cleaved after 48 h in p53 wild-type (HCT116 WT ). Besides, they thought that the cytotoxic mechanism of KP46 is an early autophagic cell death type which is reinforced by a late caspase-dependent cell death pathway [39]. Altogether, Feq 3 could mediate cell death through caspase cleavage, but it might be observed for longer exposures.…”
Section: Discussionmentioning
confidence: 99%
“…However, in 2016, Wilfinger et al demonstrated that KP-46 caused caspase-3 cleaved after 48 h in p53 wild-type (HCT116 WT ). Besides, they thought that the cytotoxic mechanism of KP46 is an early autophagic cell death type which is reinforced by a late caspase-dependent cell death pathway [39]. Altogether, Feq 3 could mediate cell death through caspase cleavage, but it might be observed for longer exposures.…”
Section: Discussionmentioning
confidence: 99%
“…Cell counting, harvesting and permeabilization were performed as in Wilfinger et al ( 2016 ), with only minor modification. Permeabilized cells were studied in either intracellular like buffer I (ICL buffer I) (130 mM KCl, 10 mM Tris-MOPS (pH 7.4), 10 μM EGTA-Tris, 1 mM KPi, 5 mM malate, 5 mM sodium glutamate, 1 μM Ca 2+ green 5N) or intracellular like buffer II (ICL buffer II) (130 mM KCl, 10 mM Tris-MOPS (pH 7.4), 10 μM EGTA-Tris, 1 mM KPi, 5 mM malate, 5 mM glutamic acid, 1 μM Ca 2+ green 5N).Importantly, these buffers are identical, with the exception that ICL I contains sodium glutamate and ICL II glutamic acid.…”
Section: Methodsmentioning
confidence: 99%
“…Cells (2 × 10 8 ) were harvested and permeabilized as described in Wilfinger et al ( 2016 ). Rhodamine123 (Molecular Probes) was used as ΔΨ probe at a concentration of 0.15 μM in ICL buffer II.…”
Section: Methodsmentioning
confidence: 99%
“…BNIP3 and NIX are two important mitochondrial stressor sensors with homology to BCL2 in the BH3 domain. Once mitophagy is triggered, BNIP3 and NIX are selectively recruited to dysfunctional mitochondria and then bound to the conserved LC3-interacting region (LIR) of LC3-II present on autophagosome to promote removal of damaged mitochondria by the autophagosome [16, 20, 21]. In addition, both BNIP3 and NIX facilitate mitophagy by promoting the release of Beclin1 from the Beclin1-Bcl2/Bcl-X complex [22].…”
Section: Introductionmentioning
confidence: 99%