Apple polyphenol phloretin inhibits type Ⅱ glucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer
Journal
Food Science and Human Wellness
Journal Volume
14
Journal Issue
4
Start Page
9250251
ISSN
2097-0765
2213-4530
Date Issued
2025-04
Author(s)
Chang, Han-Sheng
Cheng, Tzu-Chun
Tu, Shih-Hsin
Liao, Pei-Han
Lee, Yu-Ching
Ho, Chi-Tang
Chen, Li-Ching
Ho, Yuan-Soon
Abstract
This study presents novel findings on the potential of phloretin, an apple polyphenol, to enhance the effectiveness of anti-human epidermal growth factor receptor-2 (HER2) antibody therapy in HER2-positive breast cancer patients. Our research reveals that phloretin inhibits type II glucose transporter (GLUT2) activity, significantly reducing cancer cell glucose uptake. We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues, with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients. Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins, attenuate glycolysis, and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells. Furthermore, the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model, particularly in suppressing the growth of trastuzumab-resistant HER2-positive (HER2+) breast cancer. These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer, offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.
Subjects
2-intracellular domain (HER2-ICD)
Human epidermal growth factor receptor
Phloretin
Trastuzumab
Trastuzumab-resistance
Type II glucose transporter (GLUT2)
SDGs
Publisher
Tsinghua University Press
Description
Article number: 9250251
Type
journal article