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TC-13


               Longan flower water extract inhibits lung adenocarcinoma cells via

               autophagy and lysosome-mediated EGFR degradation


                                 #,1
                                                 2
                                                               2
               Tzu-Huan Hung,  Wei-Lun Qiu,  Zhi-Hu Lin,  Ai-Jung Tseng,  Tung-Yi Lin*
                                                                               2
                                                                                               ,2

               1  Crop Genetic Resources and Biotechnology Division, Taiwan Agricultural Research
                 Institute, Taichung 413008, Taiwan.
               2  Institute of Traditional Medicine, National Yang Ming Chiao Tung University. Taipei
                 112304, Taiwan.
               * E-mail: biotungyi@gmail.com

               Abstract
                  Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, remains
               associated with poor prognosis. Natural plant-derived compounds represent promising sources
               for  anticancer  drug  discovery.  In  this  study,  we  investigated  the  inhibitory  effects  and
               underlying mechanisms of longan flower water extract (LFWE) in EGFR-mutant H1975 lung
               adenocarcinoma cells. LFWE significantly reduced the viability of H1975 lung cancer cells and
               induced morphological changes. Mechanistically, LFWE activated autophagy, as indicated by
               increased  LC3-II/LC3-I  ratios  and  decreased  P62  levels,  and  promoted  lysosome-mediated
               degradation of mutant EGFR, leading to suppression of downstream mTOR and AKT signaling.
               This dual mechanism highlights LFWE’s potential to inhibit oncogenic signaling and growth
               in EGFR-TKI–resistant lung adenocarcinoma. However, LFWE also exhibited some inhibitory
               activity in non-malignant lung cells, emphasizing the need for further studies to optimize safety
               and evaluate translational applicability.

               Keywords: Longan flower water extract; Lung adenocarcinoma; Autophagy; EGFR
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