Hematoporphyrin Monomethyl Ether Enhances the Killing Action of Ultrasound on Osteosarcoma In Vivo

Tian, Zedan; Quan, Xuemou; Xu, Chuanshan; Ling, Dan; Guo, Hui; Leung, Albert Wingnang

doi:10.7863/jum.2009.28.12.1695

Cited by 31 publications

(31 citation statements)

References 15 publications

(14 reference statements)

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“…Sonodynamic therapy has been considered as a feasible strategy for treating malignancies. Our previous studies also confirmed that low-intensity ultrasound activated 5-ALA, hypocrellin B and mematoporphyrin monomethyl ether to induce the cell death of tumor cells (6)(7)(8)(9). Curcumin is a naturally ocurring spice, often prescribed in India and China to treat various diseases, such as skin, rheumatic and digestive diseases (10,11).…”

Section: Introductionmentioning

confidence: 51%

TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin

Wang

Leung

Luo

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. The present study was designed to observe the initiation of mitophagy in tumor cells after ultrasound treatment in the presence of curcumin under transmission electron microscopy. Nasopharyngeal carcinoma CNE2 cells were incubated with 10 µM curcumin and then exposed to ultrasound for 8 sec at an intensity of 0.46 W/cm 2 . Severely swollen mitochondria, disrupted mitochondria and mitophagy were noted in the CNE2 cells after ultrasound treatment in the presence of curcumin. Our findings demonstrated that ultrasound treatment in the presence of curcumin significantly initiated mitophagy in CNE2 cells, which suggests that mitophagy serves as an important event in the process of cell death of nasopharyngeal carcinoma cells. IntroductionUltrasound therapy is a safe and non-invasive therapeutic approach which shows great promise in the medical field, particularly for tumor therapy. Therapeutic ultrasound mainly includes high-and low-intensity ultrasound. At present, high-intensity focal ultrasound has been applied in the clinical management of tumors since it effectively eradicates tumor tissues through high temperatures and mechanical effects (1,2). Low-intensity ultrasound activates a sensitizer to produce sonodynamic action, which kills tumor cells directly or indirectly (3-5). Sonodynamic therapy has been considered as a feasible strategy for treating malignancies. Our previous studies also confirmed that low-intensity ultrasound activated 5-ALA, hypocrellin B and mematoporphyrin monomethyl ether to induce the cell death of tumor cells (6-9). Curcumin is a naturally ocurring spice, often prescribed in India and China to treat various diseases, such as skin, rheumatic and digestive diseases (10,11). Recently, our studies found that low-intensity ultrasound enhanced the cell death of nasopharyngeal carcinoma cells in the presence of curcumin (12,13). However, the underlying mechanisms are unclear.Necrosis, apoptosis and autophagy are the main modes of cell death which occur when tumor cells respond to chemotherapy and physical therapy (14-16). Our previous studies showed that ultrasound exposure in the presence of curcumin significantly increased the necrotic or late apoptotic rates of nasopharyngeal carcinoma cells (12). In the present study, we observed mitophagy in nasopharyngeal carcinoma CNE2 cells under transmission electron microscopy (TEM) after ultrasound treatment in the presence of curcumin. Materials and methods Sensitizer.A stock solution of curcumin from Sigma (USA) was constructed in dimethyl sulfoxide (DMSO) at a concentration of 100 mM and maintained in the dark at -20˚C until it was used.Cell culture. Nasopharyngeal carcinoma CNE2 cells were purchased from the Shanghai Biology Institute and approval was obtained by the Ethics Committee of Chongqing Medical University prior to the study. The cells were cultured in RPMI-1640 medium supplemented with 10% fetal calf serum (Gibco), 50 µg/ml penicillin, 50 µg/ml streptomycin and 10 µg/ ml neomycin. The cells were incubated at 37˚C in a humidifi...

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Section: Introductionmentioning

confidence: 51%

TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin

Wang

Leung

Luo

et al. 2011

Experimental and Therapeutic Medicine

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“…Ultrasound therapy, as a non-invasive modality, has shown promise as a novel technique in the management of tumors (5,6). To investigate the effect of low-intensity ultrasound on NPC cells, the poorly differentiated CNE2 cell line was chosen as tumor model cells for cytotoxic assay 24 h after ultrasound exposure in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…With the development of transducer design and measurement technology, ultrasound as a safe alternative and non-invasive therapeutic approach has been widely applied in medicine (5). High-intensity focal ultrasound (HIFU) produces a high temperature that directly or indirectly deactivates tumor cells/tissues and is therefore undergoing development as a noninvasive therapeutic modality in the management of cancer (6).…”

Section: Introductionmentioning

confidence: 99%

Low-intensity ultrasound-induced cellular destruction and autophagy of nasopharyngeal carcinoma cells

Wang

Leung

2011

Experimental and Therapeutic Medicine

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Abstract. Ultrasound therapy, as a non-invasive modality, has been attracting extensive attention in the management of malignant tumors. The present study aimed to investigate low-intensity ultrasound-induced cellular destruction and autophagy in nasopharyngeal carcinoma cells in vitro. Nasopharyngeal carcinoma CNE2 cells were subjected to ultrasound exposure, as tumor model cells, at an intensity of 1.35 W/cm 2 . Cytotoxicity was investigated 24 h after ultrasound treatment. Nuclear damage was observed using nuclear staining with Hoechst 33258. Mitochondrial dysfunction was measured using confocal laser scanning microscopy with rhodamine123 staining. Mitochondrial morphology and autophagy were observed using transmission electron microscopy (TEM). Low-intensity ultrasound significantly killed CNE2 cells proportional to the ultrasonic treatment time. Upon nuclear staining, nuclear condensation and typical apoptotic bodies were noted in the CNE2 cells exposed to ultrasound wave for 12 sec. A collapse in mitochondrial membrane potential was noted in the treated cells. Upon TEM, swollen mitochondria, more vacuoles and autophagy were noted after ultrasound treatment. Our findings demonstrate that low-intensity ultrasound significantly damages CNE2 cells and emphasize that autophagy may be an important event in ultrasound-induced cell death. IntroductionNasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southeast Asia, including Hong Kong. Current treatments for NPC, such as surgery, radiotherapy and chemotherapy, have serious side effects with limited success (1-4). Fortunately, continued research efforts have spawned novel therapies.With the development of transducer design and measurement technology, ultrasound as a safe alternative and non-invasive therapeutic approach has been widely applied in medicine (5). High-intensity focal ultrasound (HIFU) produces a high temperature that directly or indirectly deactivates tumor cells/tissues and is therefore undergoing development as a noninvasive therapeutic modality in the management of cancer (6). Recently, the applications of low-intensity ultrasound in tumors and vascular diseases have been widely investigated. Emerging evidence has confirmed that low-intensity ultrasound markedly inhibits the proliferation and clone formation of tumor cells through heat, mechanical effects and acoustic cavitation (7,8). Fitzgerald et al demonstrated that therapeutic ultrasound markedly decelerated cellular proliferation and decreased in-stent hyperplasia (9). Takeuchi et al reported that ultrasound energy inhibits the proliferation of mouse T lymphoma cells at an intensity of 350 mW/cm 2 and human histiocytic lymphoma cells (U-937) at an intensity of 700 mW/ cm 2 . The morphological changes included apoptosis, such as the shrinking of cells and formation of apoptotic bodies (10). However, it remains unclear which types of mechanisms are involved in these bioeffects. Recent studies have shown that autophagy is involved in the pathogenesis of tumors. The ind...

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“…In previous studies, we have investigated the combined effect of ultrasound and several sensitizers on distinct tumor cell lines (Tian et al 2009;He et al 2010;Wang et al 2010). Though various reports have demonstrated that the cytotoxicity induced by SDT might be triggered in multiple ways, the exact linkages between specific signal transduction pathways and their activation process remain unclear.…”

Section: Introductionmentioning

confidence: 99%

ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937 cells

Su¹,

Wang²,

Zhang³

et al. 2014

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Abstract. This study was to investigate the cell killing effect of chlorin-e6 (Ce6)-mediated sonodynamic therapy (SDT) on human leukemia U937 cells and explore the role of ERK signal pathway in the process. The ultrastructure changes of U937 cells induced by ultrasonic irradiation were evaluated by scanning electron microscope (SEM) and transmission electron microscope (TEM). The viability of cells was evaluated by ViaCount assay. Apoptosis was analyzed using flow cytometer as well as fluorescence microscopy with 4'-6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to analyze the expression of mitogen-activated protein kinase (MAPK). Intracellular reactive oxygen species (ROS) and mitochondria membrane potential (MMP) levels were also analyzed by flow cytometer after exposure. Our experiments showed that several distinct sonochemical effects were found after Ce6-mediated SDT treatment. Western blotting analysis indicated that the MAPK was activated. Especially, pre-treatment with ERK inhibitor U0126 could additionally enhance SDT-induced cell viability loss, early-and late-apoptotic rate, chromatin condensation, DNA fragmentation and caspase-3 activation. Besides, a mass of ROS accumulation and a conspicuous loss of mitochondrial membrane potential were detected in U937 cells. These findings suggested ERK signal pathway may deliver a survival signal which counteracts SDT-induced cell death, while combination with U0126 could significantly potentiate the SDT-induced cytotoxic effect in U937 cells.

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Hematoporphyrin Monomethyl Ether Enhances the Killing Action of Ultrasound on Osteosarcoma In Vivo

Abstract: Hematoporphyrin monomethyl ether pretreatment could substantially enhance the growth inhibition of ultrasound on osteosarcoma, which suggests that HMME is an efficient sonosensitizer, and ultrasound radiation with HMME could be developed as a new modality for treating osteosarcoma.

Cited by 31 publications

References 15 publications

TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin

TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin

Low-intensity ultrasound-induced cellular destruction and autophagy of nasopharyngeal carcinoma cells

ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937 cells

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