2. Academic Validation
  3. Polygonum barbatum extract induces ER stress-mediated UPR and autophagy to suppress colorectal cancer growth

Polygonum barbatum extract induces ER stress-mediated UPR and autophagy to suppress colorectal cancer growth

  • Toxicol Res (Camb). 2026 Jan 29;15(1):tfaf188. doi: 10.1093/toxres/tfaf188.
Pi-Kai Chang 1 2 3,  I-Chuan Yen 4,  Wei-Cheng Tsai 5,  Kuen-Tze Lin 6,  Shih-Yu Lee 1 5
Affiliations

Affiliations

  • 1 Graduate Institute of Medical Sciences, National Defense Medical University, NO. 161, Sec. 6, Minquan E. Rd., Neihu District, Taipei City 11490, Taiwan (R.O.C.).
  • 2 Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical University, No. 325, Sec. 2, Chenggong Rd., Neihu District, Taipei City 11490, Taiwan (R.O.C).
  • 3 School of Medicine, National Defense Medical University, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 11490, Taiwan (R.O.C.).
  • 4 School of Pharmacy, National Defense Medical University, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 11490, Taiwan (R.O.C.).
  • 5 Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical University, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 11490, Taiwan (R.O.C.).
  • 6 Department of Radiation Oncology, Cardinal Tien Hospital, No. 362, Zhongzheng Rd., Xindian Dist., New Taipei City 23148, Taiwan (R.O.C.); and School of Medicine, College of Medicine, Fu -Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan (R.O.C.).
PMID: 41623587 DOI: 10.1093/toxres/tfaf188
Abstract

Polygonum barbatum extract (PBE) is a traditional herbal remedy historically used for its analgesic, anti-inflammatory, and diuretic effects. However, its Anticancer potential and underlying molecular mechanisms in colorectal Cancer (CRC) remain largely unexplored. In this study, we demonstrate that PBE exerts potent cytotoxicity in CRC cells by inducing both the unfolded protein response (UPR) and Autophagy. In vitro, PBE treatment resulted in a dose-dependent reduction of cell viability and colony formation in multiple CRC cell lines. Moreover, in a HCT116 xenograft mouse model, oral administration of PBE significantly inhibited tumor growth without inducing overt toxicity. Mechanistically, PBE increased the accumulation of acidic vesicular organelles and upregulated key UPR regulators-including BiP, IRE1, and PERK-accompanied by enhanced conversion of LC3-I to LC3-II and reduced p62 levels, indicative of elevated autophagic flux. Notably, co-treatment with chloroquine, an Autophagy inhibitor, partially rescued cell viability, underscoring that Autophagy contributes to PBE-induced cell death. In addition, PBE modulated several critical signaling pathways by inhibiting EGFR, mTOR, and STAT3 while concurrently activating downstream ERK and the AMPK-ACC axis. Collectively, these results reveal that PBE triggers ER stress-mediated UPR and Autophagy to promote autophagic cell death in CRC, supporting its potential development as a novel therapeutic agent for colorectal Cancer.

Keywords

ER stress; Polygonum barbatum (PBE); autophagy; colorectal cancer (CRC); natural product; unfolded protein response (UPR).

Figures
Products