Nutritional Stress in Head and Neck Cancer Originating Cell Lines: The Sensitivity of the NRF2-NQO1 Axis

Milković, Lidija; Tomljanović, Marko; Čipak Gašparović, Ana; Novak Kujundžić, Renata; Šimunić, Dina; Konjevoda, Paško; Mojzeš, Anamarija; Đaković, Nikola; Žarković, Neven; Gall Trošelj, Koraljka (2019) Nutritional Stress in Head and Neck Cancer Originating Cell Lines: The Sensitivity of the NRF2-NQO1 Axis. Cells, 8 (9). ISSN 2073-4409

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Abstract

Nutritional stress disturbs the cellular redox- status, which is characterized by the increased generation of reactive oxygen species (ROS). The NRF2-NQO1 axis represents a protective mechanism against ROS. Its strength is cell type-specific. FaDu, Cal 27 and Detroit 562 cells differ with respect to basal NQO1 activity. These cells were grown for 48 hours in nutritional conditions (NC): (a) Low glucose–NC2, (b) no glucose, no glutamine– NC3, (c) no glucose with glutamine–NC4. After determining the viability, proliferation and ROS generation, NC2 and NC3 were chosen for further exploration. These conditions were also applied to IMR-90 fibroblasts. The transcripts/transcript variants of NRF2 and NQO1 were quantified and transcript variants were characterized. The proteins (NRF2, NQO1 and TP53) were analyzed by a western blot in both cellular fractions. Under NC2, the NRF2-NQO1 axis did not appear activated in the cancer cell lines. Under NC3, the NRF2- NQO1axis appeared slightly activated in Detroit 562. There are opposite trends with respect to TP53 nuclear signal when comparing Cal 27 and Detroit 562 to FaDu, under NC2 and NC3. The strong activation of the NRF2-NQO1 axis in IMR-90 resulted in an increased expression of catalytically deficient NQO1, due to NQO1*2/*2 polymorphism (rs1800566). The presented results call for a comprehensive exploration of the stress response in complex biological systems.

Item Type:	Article
Uncontrolled Keywords:	glucose deprivation ; glutamine deprivation ; viability ; proliferation ; ROS ; NRF2-NQO1 axis ; IMR-90 ; NQO1 transcript variants ; rs1800566 ; TP53 mutation
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type NRF2 na raskrižju epigenetičkog modeliranja, metabolizma i proliferacije stanice raka-CrossEMPATICNRF2 Koraljka Gall Trošelj IP-2016-06-4404 HRZZ
Depositing User:	Koraljka Gall Trošelj
Date Deposited:	30 Mar 2020 12:59
URI:	http://fulir.irb.hr/id/eprint/5398
DOI:	10.3390/cells8091001

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