Labile iron, ROS, and cell death are prominently induced by haemin, but not by non-transferrin-bound iron

Imoto, Shuhei; Sawamura, Tohru; Shibuya, Yukiko; Kono, Mari; Ohbuchi, Ayako; Suzuki, Takashi; Mizokoshi, Yuji; Saigo, Katsuyasu

doi:10.1016/j.transci.2021.103319

Cited by 8 publications

(1 citation statement)

References 37 publications

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“…Although Nrf2 stabilization occurs following hemin treatment, HO-1 over-activation becomes cytotoxic due to an excessive increase in iron beyond the ferritin buffering capacity. Labile iron is largely considered to be one of the main ferroptotic features, acting as an intracellular pro-oxidant that is able to trigger the Fenton reaction and, consequently, lipid peroxidation [ 6 , 62 , 63 ]. Among the several factors that influence iron metabolism, ferritin has been studied to understand the release/accumulation mechanism of labile iron.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase Modulation Drives Ferroptosis in TNBC Cells

Consoli

Sorrenti

Pittalà

et al. 2022

IJMS

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The term ferroptosis refers to a peculiar type of programmed cell death (PCD) mainly characterized by extensive iron-dependent lipid peroxidation. Recently, ferroptosis has been suggested as a potential new strategy for the treatment of several cancers, including breast cancer (BC). In particular, among the BC subtypes, triple negative breast cancer (TNBC) is considered the most aggressive, and conventional drugs fail to provide long-term efficacy. In this context, our study’s purpose was to investigate the mechanism of ferroptosis in breast cancer cell lines and reveal the significance of heme oxygenase (HO) modulation in the process, providing new biochemical approaches. HO’s effect on BC was evaluated by MTT tests, gene silencing, Western blot analysis, and measurement of reactive oxygen species (ROS), glutathione (GSH) and lipid hydroperoxide (LOOH) levels. In order to assess HO’s implication, different approaches were exploited, using two distinct HO-1 inducers (hemin and curcumin), a well-known HO inhibitor (SnMP) and a selective HO-2 inhibitor. The data obtained showed HO’s contribution to the onset of ferroptosis; in particular, HO-1 induction seemed to accelerate the process. Moreover, our results suggest a potential role of HO-2 in erastin-induced ferroptosis. In view of the above, HO modulation in ferroptosis can offer a novel approach for breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%