biostudies-literatureFurfaro ALItalian Ministry of HealthBritish Heart FoundationCOST Action BenBedPharHeart Research UKCOST action1171https://www.ebi.ac.uk/biostudies/studies/S-EPMC9219655biostudies-literatureUnknown11(6)Induction of heme oxygenase 1 (HO-1) favors immune-escape in BRAF^V600 melanoma cells treated with Vemurafenib/PLX4032 under standard cell culture conditions. However, the oxygen tension under standard culture conditions (~18 kPa O₂) is significantly higher than the physiological oxygen levels encountered in vivo. In addition, cancer cells in vivo are often modified by hypoxia. In this study, MeOV-1 primary melanoma cells bearing the BRAF^V600E mutation, were adapted to either 5 kPa O₂ (physiological normoxia) or 1 kPa O₂ (hypoxia) and then exposed to 10 μM PLX4032. PLX4032 abolished ERK phosphorylation, reduced Bach1 expression and increased HO-1 levels independent of pericellular O₂ tension. Moreover, cell viability was signAntioxidants (Basel, Switzerland)HO-1 Limits the Efficacy of Vemurafenib/PLX4032 in BRAF^V600E Mutated Melanoma Cells Adapted to Physiological Normoxia or Hypoxia.PMC9219655BenBedPhar CA20121FS/16/67/32548CA20121RG2673RF-2016-02362288Nitti MPietra GPassalacqua MIvaldo CFurfaro ALMann GELoi GfalseHO-1 Limits the Efficacy of Vemurafenib/PLX4032 in BRAF^V600E Mutated Melanoma Cells Adapted to Physiological Normoxia or Hypoxia.Induction of heme oxygenase 1 (HO-1) favors immune-escape in BRAF^V600 melanoma cells treated with Vemurafenib/PLX4032 under standard cell culture conditions. However, the oxygen tension under standard culture conditions (~18 kPa O₂) is significantly higher than the physiological oxygen levels encountered in vivo. In addition, cancer cells in vivo are often modified by hypoxia. In this study, MeOV-1 primary melanoma cells bearing the BRAF^V600E mutation, were adapted to either 5 kPa O₂ (physiological normoxia) or 1 kPa O₂ (hypoxia) and then exposed to 10 μM PLX4032. PLX4032 abolished ERK phosphorylation, reduced Bach1 expression and increased HO-1 levels independent of pericellular O₂ tension. Moreover, cell viability was sign2022-01-01T00:00:00Z2022 Jun2025-04-19T11:13:18.375Z2025-02-19T02:15:37.228ZS-EPMC92196553574006810.3390/antiox11061171