Lin, Tai‐PeiTai‐PeiLinMIN-HSIUNG PANChang, Chan‐HuaChan‐HuaChangHsiao, Kuan‐ChungKuan‐ChungHsiaoChen, Yen‐LinYen‐LinChenLai, Jui‐ShengJui‐ShengLaiYang, Wen‐ChanWen‐ChanYangCheng, Ann‐JoyAnn‐JoyChengChen, Yin‐JuYin‐JuChenYang, Chiou‐YingChiou‐YingYangHuang, Meng‐YuanMeng‐YuanHuangLiu, Ko‐JiunnKo‐JiunnLiu2026-04-162026-04-162026-03-19https://www.scopus.com/pages/publications/105033084976https://scholars.lib.ntu.edu.tw/handle/123456789/737203Article number e70142Oral cancer represents a significant global health burden owing to the limitations of current therapeutic approaches, including adverse effects and drug resistance. Phytochemicals have gained increasing attention as promising anticancer agents with multi-target effects and low toxicity. This study evaluated the anticancer potential of Phyllanthus emblica water extract (PEWE) using in vitro and in vivo models. In vitro, PEWE exhibited dose-dependent inhibition of DOK and OECM-1 oral cancer cell proliferation while sparing non-cancerous CGHNK2 cells. PEWE significantly suppressed cell migration and invasion, induced S-phase cell cycle arrest, and promoted apoptosis associated with mitochondrial dysfunction. Morphological and molecular analyses confirmed the induction of autophagy as evidenced by increased LC3 expression, decreased p62 levels, and upregulation of Rab7. RNA sequencing revealed significant modulation of key autophagy-related genes, including ITPR1, AMBRA1, and MAP1LC3B. In vivo, PEWE effectively inhibited tumor growth in xenograft and carcinogen-induced mouse oral cancer models without any apparent systemic toxicity. These findings demonstrate that PEWE exerts anticancer effects through a coordinated mechanism involving cell cycle disruption, apoptosis, and autophagy, highlighting its potential as a novel and less toxic therapeutic agent for oral cancer.trueapoptosisautophagyphytochemicalRNA sequencexenograft modeljournal article10.1002/efd2.701422-s2.0-105033084976