@conference{
author = "Markelić, Milica and Otašević, Vesna and Gudelj, Anđelija and Saksida, Tamara and Stančić, Ana and Veličković, Ksenija and Krstić, Jelena",
year = "2023",
abstract = "Recently, it has been suggested that nutrient deprivation (ND) may be effective as an adjuvant
therapy to hepatocellular carcinoma (HCC) cell treatment with sorafenib (Sfb)1. These results
suggest that ND-mediated priming of HCC cells to Sfb is positively correlated with the p53 status,
suggesting the essential role of p53 in priming of HCC cells for regulated cell death (RCD).
Preliminary data indicated morphological signs of ferroptotic RCD, so we aimed to determine whether
ferroptosis plays a role in the removal of HCC cells in vitro with respect to their p53 status. To
this end, p53 wild-type (p53WT) and p53 knockout (p53KO) HepG2 cells were grown in growth medium or
in starvation medium and treated with Sfb or with ferroptosis inducer, Rsl- 3, for 6 h.
Morphological signs of RCD and nuclear translocation (i.e. activation) of Nrf2, (master regulator
of ferroptosis-related signalling pathways), as well as protein levels of antioxidative defence
(AD) enzymes (CAT, CuZnSOD, MnSOD) and ferroptosis-related proteins (GPX4, xCT) were analysed. The
AD response to Rsl-3 treatment in p53WT cells was similar regardless of nutritional status, as the
level of all analysed enzymes increased. The response to Sfb was enhanced by ND as CAT and CuZnSOD
were elevated. p53KO cells responded quite differently, even when treated with Rsl-3, increasing
only MnSOD. Starved Sfb-treated p53KO cells even decreased expression of AD enzymes. All signs of a
proferroptotic response examined were present in starved p53WT cells (regardless of treatment):
decreased nuclear translocation of Nrf2, GPX4, and xCT expression. Nrf2 activation and GPX4
expression were also decreased in starved p53KO cells (especially upon treatment with Sfb or
Rsl-3), but accompanied by compensatory overexpressed xCT. These results may be indicative of
enhanced AD in p53KO cells and may therefore explain, at least in part, their resistance to
treatment with Sfb+ND which, as presented here, induces ferroptosis in p53WT HepG2 cells.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Proferroptotic response to nutrient deprivation in hepatocellular carcinoma cells is related to p53 status",
pages = "86",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6404"
}
