Antiproliferative activity of rosamultic acid is associated with induction of apoptosis,cell cycle arrest,inhibition of cell migration and caspase activation in human gastric cancer (SGC-7901) cells |
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| Affiliation: | 1. Southern Knights'' Laboratory LLP, University of the Ryukyus, Okinawa, Japan;2. Institute for Animal Experiments, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan;3. Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan;1. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi’an, 710069, China;2. Graduate School, The Fourth Military Medical University, 169 Changle West Road, Xi’an 710032, China;3. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi’an 710032, China;4. Department of Cardiology, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, China;5. Department of Aerospace Medicine, The Fourth Military Medical University, 169 Changle West Road, Xi’an 710032, China;6. Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi''an Jiaotong University, 277 Yanta West Road, Xi’an, 710061, China;1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China;2. Department of Chemical Engineering, Curtin University, Perth, WA, 6845, Australia |
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| Abstract: | BackgroundGastric cancer is the second leading cause of cancer related deaths after lung cancer globally. Among natural products, natural triterpenes represent a structurally diverse group of organic compounds with potent antitumor activity.PurposeThe objective of the present research work demonstrated the antiproliferative and apoptotic activity of rosamultic acid, a natural triterpenoid, in human gastric cancer (SGC-7901) cells. Its effect on cellular morphology, cell cycle arrest, DNA fragmentation and expression levels of caspase-3, caspase-8 and caspase-9 were also determined.MethodsAntiproliferative activity of rosamultic acid was evaluated by MTT assay. Phase contrast, fluorescence microscopy as well as flow cytometry using Hoechst 33342, acridine orange/ethidium bromide and Annexin V-FITC as cellular probes were used to evaluate the induction of apoptosis by rosamultic acid. Protein level expressions were analyzed by western blot analysis.ResultsThe results revealed that rosamultic acid induced dose-dependent as well as time dependent cytotoxic effects in SGC-7901 gastric cancer cells. It also led to a reduction in clonogenic activity along with inhibiting the cell migration. Characteristic features of apoptosis induced by rosamultic acid were observed and quantified. Cell cycle arrest at sub-G1 phase was induced by rosamultic acid along with downregulation of expression levels of CDK4, CDK6 and cyclin D1. Rosamultic acid also significantly led to the activation of caspase-3, -8 and -9 during the 48 h treatment along with cleaving PARP in a dose-dependent manner. DNA fragmentation following rosamultic acid treatment was also observed in these cells.ConclusionThe current study strongly reveals that rosamultic acid inhibits gastric cancer proliferation by inducing apoptosis mediated through cell cycle arrest, downregulation of cell cycle related protein expressions, inhibition of cell migration, DNA damage, and activation of caspases. |
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