Abstract
Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required.
Highlights
Breast cancer is the most frequently diagnosed cancer and one of the most deadly diseases for women [1]
At 0 μM ART, the cell viability in the ART + 5-Aminolevulinic acid (5-ALA) + US group decreased significantly compared with viability in the ART, ART + US, and ART + 5-ALA groups (p < 0.0001 for all comparisons)
ART, the cell viability in the ART + 5-ALA + US group decreased significantly compared with viability in the ART, ART + US, and ART + 5-ALA groups (p < 0.0001, p < 0.0001, and p = 0.0009, respectively)
Summary
Breast cancer is the most frequently diagnosed cancer and one of the most deadly diseases for women [1]. Molecules 2017, 22, 533 therapeutic modality for the management of malignant tumors [3,4] In support of this hypothesis, our previous report suggested that 5-ALA-based SDT induces an antitumor effect in mouse mammary tumor cells through oxidation of the mitochondrial membrane via ROS production [5]. ART is a semi-synthetic derivative of artemisinin, and is a more effective antimalarial agent [15] It exhibits anti-cancer activity against a variety of cancer cells, and has been reported to rapidly convert to ROS inside cells, thereby disrupting cellular functions [16]. ART is a promising candidate in the search for a low-toxicity compound that would increase the efficacy of 5-ALA-based SDT. 5-ALA-based SDT against mouse mammary tumors as a human cancer model in vitro
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