Hematoporphyrin Monomethyl Ether Enhances the Killing of Ultrasound on Osteosarcoma Cells Involving Intracellular Reactive Oxygen Species and Calcium Ion Elevation

Tian, Zedan; Quan, Xuemou; Leung, Albert Wingnang; Xiang, Jun; Xu, Chi

doi:10.1177/1534735410379013

Cited by 20 publications

(10 citation statements)

References 18 publications

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“…It is well known that activation of sonosensitizers can induce ROS production in cells[ 8 , 27 ] and the high levels of ROS can damage the mitochondrial membranes and oxidize mitochondrial proteins, leading to depletion of antioxidants and formation of mitochondrial permeability transition pore as well as apoptosis [ 18 , 28 ]. In addition, high levels of ROS can convert into H 2 O 2 and other toxic metabolites that release cytochrome C to activate caspase cascade, and finally lead to apoptosis[ 29 , 30 ]. Given that ultrasound alone moderately inhibited osteosarcoma cell proliferation and induced tumor cell apoptosis the mechanical effect of ultrasound may directly damage cell membranes and enhance cell membrane permeability[ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice

Zhou

et al. 2015

PLoS ONE

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ObjectiveSonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro.MethodsThe dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined.ResultsTreatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01) and reduced the viability of UMR-106 cells (p<0.05). ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both). Pre-treatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (p<0.01) and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of ΔψM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound). Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound).ConclusionsThe ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

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Section: Discussionmentioning

confidence: 99%

5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice

Zhou

et al. 2015

PLoS ONE

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“…Previous reports showed that HMME combined with ultrasonic irradiation obviously enhanced the intracellular ROS production 39 and the expression of Bax, caspase-3 and caspase-9 proteins 40 , and also displayed significant improvement on the suppression of cell viability and the induction of cell apoptosis 41 . Recent studies on human leukemia U937 cells 32 and osteosarcoma 42 revealed that HMME combined with ultrasonic irradiation might be a promising approach for cancer therapy. PpIX is a novel HPD and displays stronger anticancer activities than HP under the same ultrasonic condition because that it is much easier to be taken up by cancer cells 43 .…”

Section: Sonosensitizersmentioning

confidence: 99%

Recent advances of sonodynamic therapy in cancer treatment

Wan

Liu²,

Chen

et al. 2016

Cancer Biology &Amp; Medicine

227

157

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Sonodynamic therapy (SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.

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“…Ultrasound is known to promote membrane permeability, thus increasing intracellular drug accumulation. Previous studies have suggested that the mechanisms by which ultrasound enhances the cytotoxicity of chemotherapy drugs include increased generation of reactive oxygen species [10,11], intracellular drug accumulation [12,13], and cell membrane permeability [14,15,16]. The combined therapy concentration and sufficient exposure time were crucial to the chemotherapeutic efficacy in our study.…”

Section: Discussionmentioning

confidence: 61%

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Weng¹,

Chen

Zhao

et al. 2016

Oncol Res Treat

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Background: The objective of this study was to explore the effects of 30 kHz ultrasound on the efficacy of paclitaxel in subcutaneous breast tumors in Balb/c mice in vivo. Materials and Methods: 40 Balb/c female mice were divided into 5 groups: model control group, paclitaxel intraperitoneal (ip) group (20 mg/kg, ip, at 3 day intervals for a total of 3 doses (q3d×3)), paclitaxel intratumoral (it) group (20 mg/kg, it, q3d×3), paclitaxel intraperitoneal (20 mg/kg, ip, q3d×3) combined with low-frequency ultrasound (LFU) group, and paclitaxel intratumoral (20 mg/kg, it, q3d×3) combined with LFU group. Ultrasound parameters were 30 kHz, 200 MW intensity, 15 min, q3d×3. The antitumoral effect was determined by examining the tumor weight in subcutaneously inoculated EMT6 breast carcinoma models in Balb/c mice. All subcutaneous tumors were examined using high performance liquid chromatography (HPLC) upon completion of the experiments. Drug concentrations in the subcutaneous tumors were also analyzed using HPLC. Finally, paraffin sections of the subcutaneous tumors were made, and after hematoxylin and eosin staining, the tumor morphology was examined under a light microscope. Results: LFU combined with paclitaxel significantly restrained tumor growth in transplanted subcutaneous EMT6 tumors in Balb/c mice, and this effect correlated with increased local concentrations of paclitaxel in the tumors. Body weight measurement did not reveal significant adverse effects on the Balb/c mice during the study. Conclusion: LFU combined with paclitaxel has a significant synergistic effect in the treatment of breast cancer.

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Hematoporphyrin Monomethyl Ether Enhances the Killing of Ultrasound on Osteosarcoma Cells Involving Intracellular Reactive Oxygen Species and Calcium Ion Elevation

Cited by 20 publications

References 18 publications

5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice

5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice

Recent advances of sonodynamic therapy in cancer treatment

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

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