Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells

Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were...

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Main Authors: Diana Salvador, Verónica Bastos, Helena Oliveira
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/1/35
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author Diana Salvador
Verónica Bastos
Helena Oliveira
author_facet Diana Salvador
Verónica Bastos
Helena Oliveira
author_sort Diana Salvador
collection DOAJ
description Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.
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spelling doaj.art-5ecaaada81ab450d9b08215f016bd6972023-11-23T11:33:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-012313510.3390/ijms23010035Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma CellsDiana Salvador0Verónica Bastos1Helena Oliveira2Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, PortugalMelanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.https://www.mdpi.com/1422-0067/23/1/35skin cancermelanomahyperthermiadoxorubicincytotoxicitycell cycle arrest
spellingShingle Diana Salvador
Verónica Bastos
Helena Oliveira
Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
International Journal of Molecular Sciences
skin cancer
melanoma
hyperthermia
doxorubicin
cytotoxicity
cell cycle arrest
title Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
title_full Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
title_fullStr Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
title_full_unstemmed Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
title_short Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
title_sort hyperthermia enhances doxorubicin therapeutic efficacy against a375 and mnt 1 melanoma cells
topic skin cancer
melanoma
hyperthermia
doxorubicin
cytotoxicity
cell cycle arrest
url https://www.mdpi.com/1422-0067/23/1/35
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AT veronicabastos hyperthermiaenhancesdoxorubicintherapeuticefficacyagainsta375andmnt1melanomacells
AT helenaoliveira hyperthermiaenhancesdoxorubicintherapeuticefficacyagainsta375andmnt1melanomacells