Page 236 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-53

Natural products delay pancreatic ductal adenocarcinoma progression by

targeting ANXA2— gallic acid as an example

1
+,1
1
Bei-Yu Lin, Ping Chuang, +,#,1 Y u -Chen Liao, Yuan-Shen Hsu, Ying-Jou Wu, Chao-
2
Jung Chen, Der-Yen Lee, Y u -Huei Liu* ,1,2,3
2
2

1 Drug Development Center, China Medical University, Taichung, Taiwan
2 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
3 Department of Medical Genetics and Medical Research, China Medical University Hospital,
Taichung, Taiwan
+ These authors contributed equally to this presentation
* E-mail: yuhueiliu@mail.cmu.edu.tw

Abstract
Pancreatic ductal adenocarcinoma (PDAC), the predominant form of pancreatic cancer,
remains one of the most lethal malignancies worldwide, with limited effective treatments and a
poor prognosis. Gallic acid, a naturally occurring secondary metabolite abundant in fruits and
tea, has long been recognized for its antioxidant and anticancer properties; however, its
molecular targets remain undetermined. Here we identify that annexin A2 (ANXA2) plays a
crucial role in the reactive oxygen species (ROS) axis. Using a chemical proteomics approach,
we demonstrate that gallic acid selectively and directly interacts with ANXA2 through
hydrogen bonding to reduce glycolytic flux driven by ANXA2–S100A10 complexes. In a
syngeneic orthotopic PDAC model, oral gallic acid attenuates gut dysbiosis, enhances
antitumor immunity, reduces tumor burden, and prolongs survival. These findings highlight a
novel molecular crosstalk and establish gallic acid as a promising food-derived therapeutic lead
for PDAC, emphasizing the importance of host-microbe homeostasis in cancer therapy.

Keywords: Pancreatic ductal adenocarcinoma; Gallic acid; ANXA2; Tumor progression