Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells

Melanoma is a drug-resistant cancer, representing a serious challenge in cancer treatment. Dacarbazine (DTIC) is the standard drug in metastatic melanoma treatment, despite the poor results. Hyperthermia has been proven to potentiate chemotherapy. Hence, this work analyzed the combined action of hyp...

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Main Authors: Diana Salvador, Verónica Bastos, Helena Oliveira
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/7/3586
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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 a drug-resistant cancer, representing a serious challenge in cancer treatment. Dacarbazine (DTIC) is the standard drug in metastatic melanoma treatment, despite the poor results. Hyperthermia has been proven to potentiate chemotherapy. Hence, this work analyzed the combined action of hyperthermia and DTIC on A375 and MNT-1 cell lines. First, temperatures between 40 °C and 45 °C were tested. The effect of DTIC on cell viability was also investigated after exposures of 24, 48, and 72 h. Then, cells were exposed to 43 °C and to the respective DTIC IC10 or IC20 of each time exposure. Overall, hyperthermia reduced cell viability, however, 45 °C caused an excessive cell death (>90%). Combinational treatment revealed that hyperthermia potentiates DTIC’s effect, but it is dependent on the concentration and temperature used. Also, it has different mechanisms from the treatments alone, delaying A375 cells at the G2/M phase and MNT-1 cells at the S and G2/M phases. Intracellular reactive oxygen species (ROS) levels increased after treatment with hyperthermia, but the combined treatment showed no additional differences. Also, hyperthermia highly increased the number of A375 early apoptotic cells. These results suggest that combining hyperthermia and DTIC should be more explored to improve melanoma treatment.
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spelling doaj.art-b5132e8b0f1a46b0b717af70e24c6b852023-11-30T23:19:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237358610.3390/ijms23073586Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in 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 a drug-resistant cancer, representing a serious challenge in cancer treatment. Dacarbazine (DTIC) is the standard drug in metastatic melanoma treatment, despite the poor results. Hyperthermia has been proven to potentiate chemotherapy. Hence, this work analyzed the combined action of hyperthermia and DTIC on A375 and MNT-1 cell lines. First, temperatures between 40 °C and 45 °C were tested. The effect of DTIC on cell viability was also investigated after exposures of 24, 48, and 72 h. Then, cells were exposed to 43 °C and to the respective DTIC IC10 or IC20 of each time exposure. Overall, hyperthermia reduced cell viability, however, 45 °C caused an excessive cell death (>90%). Combinational treatment revealed that hyperthermia potentiates DTIC’s effect, but it is dependent on the concentration and temperature used. Also, it has different mechanisms from the treatments alone, delaying A375 cells at the G2/M phase and MNT-1 cells at the S and G2/M phases. Intracellular reactive oxygen species (ROS) levels increased after treatment with hyperthermia, but the combined treatment showed no additional differences. Also, hyperthermia highly increased the number of A375 early apoptotic cells. These results suggest that combining hyperthermia and DTIC should be more explored to improve melanoma treatment.https://www.mdpi.com/1422-0067/23/7/3586melanomalow-dose chemotherapymild hyperthermiacytotoxicitycell cycle
spellingShingle Diana Salvador
Verónica Bastos
Helena Oliveira
Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells
International Journal of Molecular Sciences
melanoma
low-dose chemotherapy
mild hyperthermia
cytotoxicity
cell cycle
title Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells
title_full Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells
title_fullStr Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells
title_full_unstemmed Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells
title_short Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells
title_sort combined therapy with dacarbazine and hyperthermia induces cytotoxicity in a375 and mnt 1 melanoma cells
topic melanoma
low-dose chemotherapy
mild hyperthermia
cytotoxicity
cell cycle
url https://www.mdpi.com/1422-0067/23/7/3586
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AT veronicabastos combinedtherapywithdacarbazineandhyperthermiainducescytotoxicityina375andmnt1melanomacells
AT helenaoliveira combinedtherapywithdacarbazineandhyperthermiainducescytotoxicityina375andmnt1melanomacells