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

Diana Salvador,Helena Oliveira,Verónica Bastos

doi:10.3390/ijms23010035

Diana Salvador, Helena Oliveira + Show 1 more

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https://doi.org/10.3390/ijms23010035

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Abstract

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.

Highlights

These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death
The MNT-1 cell line showed less sensibility to DOX, having a significant reduction (~8%) with exposure to the concentration of 0.5 μM for 24 h, compared to the control, which is 10-times higher than the concentration that caused a reduction in the case of A375
MNT-1 cells were demonstrated to be less sensitive to DOX than A375 cells, having higher ICs for all the tested time exposures (Table 1)

Summary

Introduction

Cancer is currently a severe health problem, being one of the main causes of death worldwide [1]. It defines a group of diseases characterized by the undisciplined growth and proliferation of abnormal cells, occurring in a variety of tissues and organs [2]. Malignant melanoma is one of the most threatening types due to its metastatic capacity, meaning that its prevalence is increasing at an alarming rate in Caucasians [4]. Melanoma is a malignant tumor that arises from melanocytes and can appear in both cutaneous and mucosal surfaces [5].

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