1. Academic Validation
  2. Ginsenoside Rg5 inhibits colorectal cancer, at least partially by blocking the lysosomal degradation of colorectal cancer cells

Ginsenoside Rg5 inhibits colorectal cancer, at least partially by blocking the lysosomal degradation of colorectal cancer cells

  • Sci Rep. 2026 Feb 4;16(1):7247. doi: 10.1038/s41598-026-37091-z.
Xiangwei Guo 1 2 3 Rongyin Sun 3 Yating Su 3 Qinghua Qin 4 Yu Liu 5 Chunhong Qiu 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
  • 2 National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.
  • 3 Department of Cell Biology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
  • 4 Department of Biology, Technical University of Darmstadt, 64287, Darmstadt, Germany.
  • 5 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.
  • 6 Department of Cell Biology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. [email protected].
Abstract

The development of novel low-toxicity, high-efficacy therapeutics for colorectal Cancer is urgently needed, given its global burden of approximately two million new cases and one million deaths annually. In the present study, we demonstrated for the first time that Ginsenoside Rg5 (Rg5), a small-molecule compound isolated from red ginseng, significantly inhibited tumor growth of colorectal Cancer in mouse models. In addition, the levels of autophagy-related proteins, including LC3-II and p62, were significantly increased in tumors from Rg5-treated mice. Further mechanistic investigations revealed that Rg5 suppresses lysosomal degradation in colorectal Cancer cells through inhibition of ATP6V1A (a key subunit of V-ATPase), consequently blocking autophagic flux. This impairment of Autophagy ultimately induces Apoptosis in colorectal Cancer cells and inhibits tumor progression. This study provides evidence that Rg5 functions as an Autophagy inhibitor, laying the foundation for its application in colorectal cancer Adjuvant therapy.

Keywords

Apoptosis; Autophagolysosome; Autophagy; Colorectal cancer; Ginsenoside Rg5; Lysosomal degradation.

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