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      The effect of aloe emodin–encapsulated nanoliposome‐mediated r‐caspase‐3 gene transfection and photodynamic therapy on human gastric cancer cells

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          Abstract

          Gastric carcinoma ( GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy ( PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin ( AE)–encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer ( PS). AE‐encapsulated nanoliposomes (nano‐ AE) were prepared by reverse evaporation method. Electron microscopy and nano‐ ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase‐3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species ( ROS) contents were measured by DCFHDA staining. Outcomes demonstrated that the nano‐ AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r‐caspase‐3 was transfected had higher protein expression of the caspase‐3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano‐ AE‐mediated PDT in an energy‐dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm 2). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano‐ AE PDT group had quadrupled in SGC‐7901 cells as early as 1 h after PDT, while it is similar to the group of nano‐ AE transfection and PDT. Nano‐ AE‐mediated r‐caspase‐3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human gastric cancer cells.

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          Most cited references17

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          Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors.

          Here we report that aloe-emodin (AE), a hydroxyanthraquinone present in Aloe vera leaves, has a specific in vitro and in vivo antineuroectodermal tumor activity. The growth of human neuroectodermal tumors is inhibited in mice with severe combined immunodeficiency without any appreciable toxic effects on the animals. The compound does not inhibit the proliferation of normal fibroblasts nor that of hemopoietic progenitor cells. The cytotoxicity mechanism consists of the induction of apoptosis, whereas the selectivity against neuroectodermal tumor cells is founded on a specific energy-dependent pathway of drug incorporation. Taking into account its unique cytotoxicity profile and mode of action, AE might represent a conceptually new lead antitumor drug.
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            Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma

            This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics, photosensitizers for PDT in patients with esophageal disease. Finally, we discuss its utility and limitations in this setting.
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              Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells.

              Aloe-emodin, one of the anthraquinones, has been shown to have anticancer activity in different kinds of human cancer cell lines. Therefore, the purpose of this study was to investigate the anti-cancer effect of aloe-emodin on human tongue squamous carcinoma SCC-4 cells. The results indicated that aloe-emodin induced cell death through S-phase arrest and apoptosis in a dose- and time-dependent manner. Treatment with 30 microM of aloe-emodin led to S-phase arrest through promoted p53, p21 and p27, but inhibited cyclin A, E, thymidylate synthase and Cdc25A levels. Aloe-emodin promoted the release of apoptosis-inducing factor (AIF), endonuclease G (Endo G), pro-caspase-9 and cytochrome c from the mitochondria via a loss of the mitochondrial membrane potential (DeltaPsi(m)) which was associated with a increase in the ratio of B-cell lymphoma 2-associated X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) and activation of caspase-9 and -3. The free radical scavenger N-acetylcysteine (NAC) and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis. Aloe-emodin thus induced apoptosis in the SCC-4 cells through the Fas/death-receptor, mitochondria and caspase cascade. Aloe-emodin could be a novel chemotherapeutic drug candidate for the treatment of human tongue squamous cancer in the future.
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                Author and article information

                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                21 December 2015
                February 2016
                : 5
                : 2 ( doiID: 10.1002/cam4.2016.5.issue-2 )
                : 361-369
                Affiliations
                [ 1 ] Department of RehabilitationThe First Affiliated Hospital of Chongqing Medical University ChongqingChina
                [ 2 ] Department of gastroenterologyChinese Medicine Hospital of Longquan ChengduChina
                [ 3 ] Department of gastroenterologyThe First Affiliated Hospital of Chongqing Medical University ChongqingChina
                Author notes
                [*] [* ] Correspondence

                Ding‐Qun Bai, Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Tel: 86 13808380876; Fax: 021 89012936; E‐mail:  baidingqun2014@ 123456163.com

                Article
                CAM4584
                10.1002/cam4.584
                4735781
                26686868
                33b44f43-80d8-40cc-bba9-daf32164ed24
                © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 July 2015
                : 26 September 2015
                : 11 October 2015
                Page count
                Pages: 9
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81101692
                Funded by: Natural Science Foundation Project of CQ CSTC
                Award ID: 2011BB5136
                Categories
                Original Research
                Cancer Biology
                Original Research
                Custom metadata
                2.0
                cam4584
                February 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:02.02.2016

                Oncology & Radiotherapy
                aloe emodin,nanoliposome,photodynamic therapy,transfection
                Oncology & Radiotherapy
                aloe emodin, nanoliposome, photodynamic therapy, transfection

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