Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy

Abstract

Background: Sonodynamic therapy (SDT) was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX), had been demonstrated. Here we investigate the effects of PpIXmediated SDT on macrophages, which are the main culprit in progression of atherosclerosis. Methods and results: Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 µg/mL PpIX and five minutes of sonication. Production of intracellular singlet oxygen and secondary disruption of the cytoskeleton were also observed after SDT with PpIX. Conclusion: PpIX-mediated SDT had apoptotic effects on THP-1 macrophages via generation of intracellular singlet oxygen and disruption of the cytoskeleton. PpIX-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque.

Sonodynamic effect of hematoporphyrin monomethyl ether on ligature-induced periodontitis in rats

“… 7 , 12 Recently, several experimental studies demonstrated that SDT plays an important role in the induction of apoptosis and necrosis of inflammatory cells, such as THP-1 and U937. 8 , 9 However, its applicability for the prevention of periodontitis and feasibility for the treatment of periodontal diseases has rarely been reported. In the present study, we explored the histological evaluation of the sonodynamic efficacy of HMME on experimentally induced periodontal disease in rats.…”

“… 7 Several experimental studies showed satisfactory results using SDT to kill inflammatory cells, such as THP-1 and U937. 8 , 9 The lethal sonosensitization of these cells must involve changes in the membranes and/or plasma membrane proteins and DNA damage mediated by reactive oxygen species (ROS). 10 However, to date, SDT has not been applied to periodontitis.…”

Cytotoxic Effect of Protoporphyrin IX to Human Leukemia U937 Cells under Ultrasonic Irradiation

“…Under normal condition, PpIX and heme (iron-PpIX) are vital for cellular homestasis, but free uncommitted pools of these molecules are highly cytotoxic [9]. Studies have found that the concentration of PpIX in cell or tissue could be increased not only by administration of its precursor δ-aminolevulinic acid (5-ALA) but also PpIX itself [10,11,12]. Obviously, the exogenous PpIX leads to more visible cytotoxicity than endogenous PpIX in SDT [10].…”

“…The process of apoptosis induced by SDT may involve SDT induced damage on several cellular components, such as plasma membrane, mitochondria, nucleus and chromatin. On the other hands, some observations indicate that SDT may induce tumor cell apoptosis through the influence of genes regulating apoptosis [4,12,13,14]. However, since the efficacy of SDT may be influenced by multiple factors, including the nature of the biological model, the sonosensitizer, and the ultrasonic parameters, the detailed mechanism of SDT is unclear until now.…”

Non-Lethal Sonodynamic Therapy Inhibits Atherosclerotic Plaque Progression in ApoE-/- Mice and Attenuates ox-LDL-mediated Macrophage Impairment by Inducing Heme Oxygenase-1

“…In a rabbit model of AS, low-intensity SDT stabilized early atherosclerotic plaques by inducing macrophage apoptosis and apoptotic cell clearance [14]. However, the underlying mechanism of SDT in treating AS is still unclear [8, 9, 15, 16]. Considering that ultrasound intensity attenuates as sound waves pass through human tissue towards an atherosclerotic plaque and that macrophage survival state in human atherosclerotic plaques varies [17], so the effects of very low-intensity SDT (non-lethal SDT, NL-SDT) in AS should be assessed.…”