Department of Drug and Health Science, University of Catania, 95125 Catania, Italy.
CERNUT-Research Centre on Nutraceuticals and Health Products, University of Catania, 95125 Catania, Italy.
Int J Mol Sci. 2022 May 20;23(10):5709. doi: 10.3390/ijms23105709.
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.
铁死亡是一种独特的程序性细胞死亡（PCD）方式，主要表现为广泛的铁依赖性脂质过氧化。最近，铁死亡被认为是治疗多种癌症（包括乳腺癌）的一种潜在新策略。特别是在乳腺癌的亚型中，三阴性乳腺癌（TNBC）被认为是最具侵袭性的，传统药物无法提供长期疗效。在这种情况下，我们的研究旨在探讨乳腺癌细胞系中铁死亡的机制，并揭示血红素加氧酶（HO）在这一过程中的调节意义，为新的生化方法提供依据。通过 MTT 试验、基因沉默、Western blot 分析以及活性氧（ROS）、谷胱甘肽（GSH）和脂质过氧化物（LOOH）水平的测量，评估 HO 对 BC 的影响。为了评估 HO 的意义，我们采用了不同的方法，使用两种不同的 HO-1 诱导剂（血红素和姜黄素）、一种众所周知的 HO 抑制剂（SnMP）和一种选择性 HO-2 抑制剂。研究结果表明 HO 参与了铁死亡的发生；特别是 HO-1 的诱导似乎加速了这一过程。此外，我们的结果还提示 HO-2 在 erastin 诱导的铁死亡中可能发挥作用。综上所述，HO 在铁死亡中的调节可能为乳腺癌的治疗提供一种新方法。
