Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis

Melanoma is the most aggressive and life-threatening skin cancer type. The melanoma genome is the most frequently mutated, with the <i>BRAF</i> mutation present in 40–60% of melanoma cases. <i>BRAF</i>-mutated melanomas are characterized by a higher aggressiveness and progres...

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Main Authors: Rafaela Dias Oliveira, Sónia Pires Celeiro, Catarina Barbosa-Matos, Ana Sofia Freitas, Susana M. Cardoso, Marta Viana-Pereira, Cristina Almeida-Aguiar, Fátima Baltazar
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/27/11/3533
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author Rafaela Dias Oliveira
Sónia Pires Celeiro
Catarina Barbosa-Matos
Ana Sofia Freitas
Susana M. Cardoso
Marta Viana-Pereira
Cristina Almeida-Aguiar
Fátima Baltazar
author_facet Rafaela Dias Oliveira
Sónia Pires Celeiro
Catarina Barbosa-Matos
Ana Sofia Freitas
Susana M. Cardoso
Marta Viana-Pereira
Cristina Almeida-Aguiar
Fátima Baltazar
author_sort Rafaela Dias Oliveira
collection DOAJ
description Melanoma is the most aggressive and life-threatening skin cancer type. The melanoma genome is the most frequently mutated, with the <i>BRAF</i> mutation present in 40–60% of melanoma cases. <i>BRAF</i>-mutated melanomas are characterized by a higher aggressiveness and progression. Adjuvant targeted treatments, such as BRAF and MEK inhibitors, are added to surgical excision in <i>BRAF</i>-mutated metastatic melanomas to maximize treatment effectiveness. However, resistance remains the major therapeutic problem. Interest in natural products, like propolis, for therapeutic applications, has increased in the last years. Propolis healing proprieties offer great potential for the development of novel cancer drugs. As the activity of Portuguese propolis has never been studied in melanoma, we evaluated the antitumoral activity of propolis from Gerês (G18.EE) and its fractions (<i>n</i>-hexane, ethyl acetate (EtOAc), and <i>n</i>-butanol) in A375 and WM9 melanoma cell lines. Results from DPPH•/ABTS• radical scavenging assays indicated that the samples had relevant antioxidant activity, however, this was not confirmed in the cell models. G18.EE and its fractions decreased cell viability (SRB assay) and promoted ROS production (DHE/Mitotracker probes by flow cytometry), leading to activation of apoptotic signaling (expression of apoptosis markers). Our results suggest that the <i>n</i>-BuOH fraction has the potential to be explored in the pharmacological therapy of melanoma.
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spelling doaj.art-94db6ed94baf42799be1a514ee296f972023-11-23T14:30:19ZengMDPI AGMolecules1420-30492022-05-012711353310.3390/molecules27113533Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of ApoptosisRafaela Dias Oliveira0Sónia Pires Celeiro1Catarina Barbosa-Matos2Ana Sofia Freitas3Susana M. Cardoso4Marta Viana-Pereira5Cristina Almeida-Aguiar6Fátima Baltazar7CBMA−Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, PortugalCBMA−Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, 4710-057 Braga, PortugalLAQV-REQUIMTE & Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, PortugalCBMA−Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, PortugalMelanoma is the most aggressive and life-threatening skin cancer type. The melanoma genome is the most frequently mutated, with the <i>BRAF</i> mutation present in 40–60% of melanoma cases. <i>BRAF</i>-mutated melanomas are characterized by a higher aggressiveness and progression. Adjuvant targeted treatments, such as BRAF and MEK inhibitors, are added to surgical excision in <i>BRAF</i>-mutated metastatic melanomas to maximize treatment effectiveness. However, resistance remains the major therapeutic problem. Interest in natural products, like propolis, for therapeutic applications, has increased in the last years. Propolis healing proprieties offer great potential for the development of novel cancer drugs. As the activity of Portuguese propolis has never been studied in melanoma, we evaluated the antitumoral activity of propolis from Gerês (G18.EE) and its fractions (<i>n</i>-hexane, ethyl acetate (EtOAc), and <i>n</i>-butanol) in A375 and WM9 melanoma cell lines. Results from DPPH•/ABTS• radical scavenging assays indicated that the samples had relevant antioxidant activity, however, this was not confirmed in the cell models. G18.EE and its fractions decreased cell viability (SRB assay) and promoted ROS production (DHE/Mitotracker probes by flow cytometry), leading to activation of apoptotic signaling (expression of apoptosis markers). Our results suggest that the <i>n</i>-BuOH fraction has the potential to be explored in the pharmacological therapy of melanoma.https://www.mdpi.com/1420-3049/27/11/3533Portuguese propoliscancermelanomaantitumoral activityantioxidant activitypro-oxidant activity
spellingShingle Rafaela Dias Oliveira
Sónia Pires Celeiro
Catarina Barbosa-Matos
Ana Sofia Freitas
Susana M. Cardoso
Marta Viana-Pereira
Cristina Almeida-Aguiar
Fátima Baltazar
Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
Molecules
Portuguese propolis
cancer
melanoma
antitumoral activity
antioxidant activity
pro-oxidant activity
title Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
title_full Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
title_fullStr Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
title_full_unstemmed Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
title_short Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
title_sort portuguese propolis antitumoral activity in melanoma involves ros production and induction of apoptosis
topic Portuguese propolis
cancer
melanoma
antitumoral activity
antioxidant activity
pro-oxidant activity
url https://www.mdpi.com/1420-3049/27/11/3533
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