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

Abstract

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...

Natural Compounds as Regulators of the Cancer Cell Metabolism

“…Moreover, it has been demonstrated that curcumin activates mitophagy. This finding underlines the importance of mitophagy in the process of cell death of nasopharyngeal carcinoma cells [118]. …”

Effects of Plant and Animal Natural Products on Mitophagy

“…Several curcumin-mediated pharmacological effects have been described, including antiinflammatory [36][37][38], immunomodulatory [39], antitumor and chemosensitizing [40][41][42], anti-ischemic [43], hepatoprotective [44], relaxant [45], and antiasthmatic effects [46,47]. Effects of curcumin (10 μM) on the viability of nasopharyngeal carcinoma CNE2 cells exposed to ultrasound were investigated by Wang et al In their study, ultrastructure of mitochondria was disrupted and mitophagy was induced by curcumin in CNE2 cells [48].…”

A Review of Low-Intensity Ultrasound for Cancer Therapy

“…The therapy's effectiveness has also been demonstrated in more deeply located tumors including those of the central nervous system (Ohmura et al 2011; Gao et al 2013; Jeong et al 2012). Post-therapy histologic studies have consistently shown damage to the ultrastructure of the cancer cells including destruction of cell membranes, mitochondrial swelling and chromatin condensation (Liu et al 2006[b], 2007[a, b], 2008; Wang et al 2008[a], 2011[c], 2012[b]); it was considered that these changes induced by the therapy may have mediated cancer cell death. Combining photodynamic therapy with sonodynamic therapy had a synergistic effect in solid tumors with additional post-therapy tumor necrosis, inhibition of tumor growth and increased survival times (Jin et al 2000; Tserkovsky et al 2012).…”