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Investigation of the inhibitory effect of capsaicin on Epstein-Barr virus lytic reactivation in gastric cancer using proteomics and bioinformatics approaches |
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| รหัสดีโอไอ | |
| Title | Investigation of the inhibitory effect of capsaicin on Epstein-Barr virus lytic reactivation in gastric cancer using proteomics and bioinformatics approaches |
| Creator | Nutchanat Chatchawankanpanich |
| Contributor | Chanitchote Piyapittayanan, Advisor |
| Publisher | Thammasat University |
| Publication Year | 2568 |
| Keyword | Capsaicin, EBV lytic reactivation, Gastric cancer, Proteomics, Molecular docking |
| Abstract | Gastric cancer (GC) is a prevalent malignancy associated with Epstein-Barr virus (EBV) infection. EBV lytic reactivation has been proposed as a key contributing factor in both carcinogenesis and GC progression. Therefore, identifying effective compounds that can inhibit EBV lytic reactivation and suppress GC is of considerable clinical importance. Capsaicin, a bioactive phytochemical, possesses diverse pharmacological properties, including potent antiviral and anticancer activities. This study evaluated the inhibitory effects of capsaicin on EBV lytic reactivation and GC progression and to identify potential target proteins using integrated proteomics, network-based, and molecular docking approaches. The results showed that capsaicin inhibited cell growth in dose-dependent manner in both human gastric adenocarcinoma (AGS and AGS-EBV) cells. Importantly, capsaicin significantly inhibited EBV lytic reactivation and reduced virion production in AGS-EBV cells. Moreover, capsaicin suppressed cell migration and invasion by down-regulating key EMT markers, including CDH2, VIM, TWIST1, SNAIL1, ZEB1, and up-regulating CDH1, indicating a robust inhibitory effect on the EMT process. While capsaicin induced apoptosis in AGS cells, AGS-EBV cells exhibited a greater resistance to cell death. Proteomic analysis combined with network-based and molecular docking approaches suggested that capsaicin interacts with several hub proteins involved in chaperone activity, cytoskeletal organization, translation, stress signaling and cell survival, including HSP90AB1, ANXA2, EEF1A1, RACK1, MYH9, PARP8, and PPIA. Collectively, this study demonstrates that capsaicin suppresses both EBV reactivation and GC progression through multiple molecular mechanisms. These findings support the further development of capsaicin as a promising therapeutic agent for GC and other EBV-associated malignancies. |