Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.
Ultrason Sonochem. 2016 Nov ;33:26-36. Epub 2016 Apr 11. PMID: 27245953
Yixiang Li, Pan Wang, Xiyang Chen, Jianmin Hu, Yichen Liu, Xiaobing Wang, Quanhong Liu
Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy.
Article Published Date : Oct 31, 2016
Clinical trial of blood-brain barrier disruption by pulsed ultrasound.
Sci Transl Med. 2016 Jun 15 ;8(343):343re2. PMID: 27306666
Alexandre Carpentier, Michael Canney, Alexandre Vignot, Vincent Reina, Kevin Beccaria, Catherine Horodyckid, Carine Karachi, Delphine Leclercq, Cyril Lafon, Jean-Yves Chapelon, Laurent Capelle, Philippe Cornu, Marc Sanson, Khê Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih
The blood-brain barrier (BBB) limits the delivery of systemically administered drugs to the brain. Methods to circumvent the BBB have been developed, but none are used in standard clinical practice. The lack of adoption of existing methods is due to procedural invasiveness, serious adverse effects, and the complications associated with performing such techniques coincident with repeated drug administration, which is customary in chemotherapeutic protocols. Pulsed ultrasound, a method for disrupting the BBB, was shown to effectively increase drug concentrations and to slow tumor growth in preclinical studies. We now report the interim results of an ultrasound dose-escalating phase 1/2a clinical trial using an implantable ultrasound device system, SonoCloud, before treatment with carboplatin in patients with recurrent glioblastoma (GBM). The BBB of each patient was disrupted monthly using pulsed ultrasound in combination with systemically injected microbubbles. Contrast-enhanced magnetic resonance imaging (MRI) indicated that the BBB was disrupted at acoustic pressure levels up to 1.1 megapascals without detectable adverse effects on radiologic (MRI) or clinical examination. Our preliminary findings indicate that repeated opening of the BBB using our pulsed ultrasound system, in combination with systemic microbubble injection, is safe and well tolerated in patients with recurrent GBM and has the potential to optimize chemotherapy delivery in the brain.
Article Published Date : Jun 14, 2016
Therapeutic Ultrasound and Treadmill Training Suppress Peripheral Nerve Injury Induced-Pain in Rats.
Phys Ther. 2016 Apr 28. Epub 2016 Apr 28. PMID: 27126126
Ching-Hsia Hung, Po-Ching Huang, Jann-Inn Tzeng, Jhi-Joung Wang, Yu-Wen Chen
BACKGROUND: Although evidence suggests that therapeutic ultrasound (TU) in combination with treadmill training (TT) suppresses nerve injury-associated pain, the molecular mechanisms for this action are not clear.
OBJECTIVE: The purpose of this research was to study the possible beneficial effects of TU and TT, alone and in combination, on two clinical indicators of neuropathic pain and to correlate these findings with changes in inflammatory mediators within the spinal cord. Our experimental model used the well-known chronic constriction injury (CCI) of the rat sciatic nerve.
DESIGN: An experimental study.
METHODS: Each group contained 10 rats. Group 1 underwent only the CCI procedure. Group 2 underwent a sham-operation where the sciatic nerve was exposed but not ligated. Group 3 had the sham-operation followed by both TT and TU. Groups 4, 5, and 6 underwent the CCI procedure followed by TT alone, TU alone, and both the TT and TU interventions, respectively. Heat and mechanical sensitivity, interleukin-6 (IL-6), IL-10, and ionized calcium binding adaptor molecule 1 (iba-1) were evaluated.
RESULTS: Compared to Group 1 animals, TT and/or TU produced smaller decreases in mechanical withdrawal threshold and heat withdrawal latencies. The combination of TT and TU was more effective than either treatment alone. In addition, rats who received these treatments did not express the upregulation of IL-6 and iba-1 in their spinal cords on postoperative days 14 and 28, as was found in the Group 1 animals.
LIMITATIONS: These experimental findings may not be generalizable to humans.
CONCLUSIONS: The combination of TU + TT reduces neuropathic pain more than either modality alone. This beneficial effect appears related to down-regulation of pro-inflammatory IL-6 and iba-1, while up-regulating the anti-inflammatory IL-10.
Article Published Date : Apr 27, 2016
Ultrasound induces cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin.
Ultrasonics. 2011 Feb;51(2):165-70. Epub 2010 Aug 4. PMID: 20728195
Xinna Wang, Xinshu Xia, Albert Wingnang Leung, Junyan Xiang, Yuan Jiang, Ping Wang, Jing Xu, Heping Yu, Dingqun Bai, Chuanshan Xu
Department of Photodynamic and Sondynamic Therapy, The Second Affiliated Hospital, The Chongqing Medical University, Chongqing, China.
OBJECTIVES: Curcumin, a natural pigment from the traditional Chinese herb, has shown promise as an efficient enhancer of ultrasound. The present study aims to investigate ultrasound-induced cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin in vitro.
METHODS: Nasopharyngeal carcinoma cell line CNE2 cells were incubated by 10μm curcumin and then were treated by ultrasound for 8s at the intensity of 0.46W/cm(2). Cytotoxicity was evaluated using MTT assay and light microscopy. Mitochondrial damage was analyzed using a confocal laser scanning microcopy with Rhodamine 123 and ultrastructural changes were observed using a transmission electron microscopy (TEM).
RESULTS: MTT assay showed that cytotoxicity induced by ultrasound treatment alone and curcumin treatment alone was 18.16±2.37% and 24.93±8.30%, respectively. The cytotoxicity induced by the combined treatment of ultrasound and curcumin significantly increased up to 86.67±7.78%. TEM showed that microvillin disappearance, membrane blebbing, chromatin condensation, swollen mitochondria, and mitochondrial myelin-likebody were observed in the cells treated by ultrasound and curcumin together. The significant collapse of mitochondrial membrane potential (MMP) was markedly observed in the CNE2 cells after the combined treatment of curcumin and ultrasound.
CONCLUSIONS: Our findings demonstrated that ultrasound sonication in the presence of curcumin significantly killed the CNE2 cells and induced ultrastructural damage and the dysfunction of mitochondria, suggesting that ultrasound treatment remarkably induced cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin.
Article Published Date : Feb 01, 2011
Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin.
Integr Cancer Ther. 2010 Aug 11. Epub 2010 Aug 11. PMID: 20702493
Xinna Wang, Xinshu Xia, Chuanshan Xu, Jing Xu, Ping Wang, Junyan Xiang, Dingqun Bai, Albert Wingnang Leung
Objectives. Curcumin, a natural pigment from a traditional Chinese herb, has been attracting extensive attention. The present study aims to investigate cell death of nasopharyngeal carcinoma (NPC) cells induced by ultrasound sonication in the presence of curcumin in vitro. METHODS: The NPC cell line CNE2 was chosen as a tumor model, and curcumin concentration was kept constant at 10 muM while the cells were subjected to ultrasound exposure for 8 s at an intensity of 0.46 W/cm(2). Cell death was evaluated using flow cytometry with annexinV-FITC and propidium iodine staining, and nuclear staining with Hoechst 33258. Mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were analyzed using flow cytometry with rhodamine 123 and dichlorodihydrofluorecein diacetate staining. RESULTS: Flow cytometry showed that the combination of ultrasound and curcumin significantly increased the necrotic or late apoptotic rate by up to 31.37% compared with the controls. Nuclear condensation was observed in the nuclear staining, and collapse of DeltaPsim and ROS increase were found in the CNE2 cells after the treatment with curcumin and ultrasound. CONCLUSIONS: The findings demonstrate that the presence of curcumin significantly enhances the ultrasound-induced cell death and ROS level, and induces the collapse of DeltaPsim, suggesting that ultrasound sonication can increase the cell death of NPC cells in the presence of curcumin and that the treatment using curcumin and ultrasound together is a potential therapeutic modality in the management of malignant tumors.
Article Published Date : Aug 11, 2010
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