Nanolive technology reveals ferroptosis execution in an aggressive human prostate cancer model

Ferroptosis is a new type of regulated cell death that was formally identified in 2012 [1]. It is an iron-dependent, non-apoptotic mode of cell death that is strongly linked to lipid metabolism. Since its discovery, Ferroptosis has been identified as a key regulator of occurrence and development in numerous diseases [2]. Inducing ferroptosis has also been shown to be effective in the treatment of highly malignant carcinomas [3].

Identifying the morphological changes that characterize ferroptosis is imperative to understand the pervasiveness of this type of cell death. Nothing is currently known about the morphology and/or distribution of lipid droplets during ferroptosis, despite the critical importance of lipid peroxidation in this type of cell death [4]. Nanolive’s 3D Cell Explorer (see here) can image lipid droplets without the addition of labels, for long periods of time (from days to weeks) and so we set about investigating this question.

This video was collected during a demonstration conducted at the Department of Pathology, in the University of Göttingen (Germany). Assistant Professor Dr. Vivek Venkataramani is the first to apply cutting-edge Nanolive imaging technology to investigate ferroptosis. He induced ferroptosis in PC3 cells (an androgen-independent prostate cancer cell line) using RNA-interference (RNAi) with the selective glutathione peroxidase 4 inhibitor, RSL-3 and then imaged the cells over a period of 24 h, at an acquisition rate of 1 image every 10 min.

In the footage, we can observe the morphological changes the cells undergo during Ferroptosis. The cell contracts and then begins to swell. Perinuclear lipid assembly is observed immediately before ferroptosis occurs. Once the process is complete, lipid droplets are redistributed. These spatial shifts in lipid droplet distribution are, to the best of our knowledge, novel observations. The importance of our observations needs to be investigated experimentally, but this video highlights the capacity of our technology to generate novel morphological observations and hypotheses.

 

  1. Dixon, S. J. et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).
  2. Li, J. et al. Ferroptosis: past, present and future. Cell Death Dis. 11, (2020).
  3. Belavgeni, A. et al. Exquisite sensitivity of adrenocortical carcinomas to induction of ferroptosis. Proc. Natl. Acad. Sci. U. S. A. 116, 22269–22274 (2019).
  4. Yang, W. S. & Stockwell, B. R. Ferroptosis: death by lipid peroxidation. Trends Cell Biol. 26, 165–176 (2016).

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