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Endoplasmic reticulum stress is involved in response of human laryngeal carcinoma cells to carboplatin but is absent in carboplatin resistant cells

Brozović, Anamaria; Vuković, Lidija; Stupin Polančac, Darija; Arany, Istvan; Köberle, Beate; Fritz, Gerhard; Fiket, Željka; Majhen, Dragomira; Ambriović-Ristov, Andreja; Osmak, Maja (2013) Endoplasmic reticulum stress is involved in response of human laryngeal carcinoma cells to carboplatin but is absent in carboplatin resistant cells. PLoS ONE, 8 (9). e76397/1-e76397/12. ISSN 1932-6203

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The major obstacle of successful tumor treatment with carboplatin (CBP) is the development of drug resistance. In the present study, we found that following treatment with CBP the amount of platinum which enters the human laryngeal carcinoma (HEp2)-derived CBP-resistant (7T) cells is reduced relative to the parental HEp2. As a consequence, the formation of reactive oxidative species (ROS) is reduced, the induction of endoplasmic reticulum (ER) stress is diminished, the amount of inter- and intrastrand cross-links is lower, and the induction of apoptosis is depressed. In HEp2 cells, ROS scavenger tempol, inhibitor of ER stress salubrinal, as well as gene silencing of ER stress marker CCAAT/enhancer-binding protein (CHOP) increases their survival and renders them as resistant to CBP as 7T cell subline but did not influence the survival of 7T cells. Our results suggest that in HEp2 cells CBP-induced ROS is a stimulus for ER stress. To the contrary, despite the ability of CBP to induce formation of ROS and activate ER stress in 7T cells, the cell death mechanism in 7T cells is independent of ROS induction and activation of ER stress. The novel signaling pathway of CBP-driven toxicity that was found in the HEp2 cell line, i.e. increased ROS formation and induction of ER stress, may be predictive for therapeutic response of epithelial cancer cells to CBP-based therapy.

Item Type: Article
Uncontrolled Keywords: apoptosis; carboplatin; drug resistance; endoplasmic reticulum stress; reactive oxidative species; tumor cells
Subjects: NATURAL SCIENCES > Geology
Divisions: Division of Molecular Biology
Project titleProject leaderProject codeProject type
Stanični odgovor na citotoksične spojeve i razvoj otpornosti[34303] Maja Osmak098-0982913-2748MZOS
Povećanje transdukcije adenovirusnih vektora i otpornost stanica na citostatike[173311] Andreja Ambriović Ristov098-0982913-2850MZOS
Biogeokemija metala u sedimentacijskim sustavima i tlima Hrvatske[85574] Goran Kniewald098-0982934-2715MZOS
Depositing User: Anamaria Brozović
Date Deposited: 08 Jul 2015 12:04
DOI: 10.1371/journal.pone.0076397

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