2. Academic Validation
  3. Lasiokaurin suppresses breast cancer growth by blocking autophagic flux and regulating cellular energy homeostasis

Lasiokaurin suppresses breast cancer growth by blocking autophagic flux and regulating cellular energy homeostasis

  • Biochem Pharmacol. 2025 Aug 7;242(Pt 3):117212. doi: 10.1016/j.bcp.2025.117212.
Rui Huang 1,  Ping Jin 2,  Jun Cao 3,  Jinguo Liu 4,  Zhen Liu 5,  Jianhua Chen 6
Affiliations

Affiliations

  • 1 Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200800, PR China.
  • 2 State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan and Key Laboratory of Industrial Microbial Fermentation Engineering of Yunnan Province, School of Life Sciences, Yunnan University, Kunming 650206, PR China.
  • 3 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
  • 4 Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China; Tongji University Cancer Center, Shanghai 200072, PR China.
  • 5 Guizhou Provincial People's Hospital, Guiyang 550002, PR China; School of Medicine, Guizhou University, Guiyang 550002, PR China. Electronic address: zhenliu@gzu.edu.cn.
  • 6 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, PR China. Electronic address: jianhua_chen@fudan.edu.cn.
PMID: 40782951 DOI: 10.1016/j.bcp.2025.117212
Abstract

Breast Cancer is the most prevalent malignancy and the second leading cause of cancer-related mortality among women worldwide. Lasiokaurin, a natural compound isolated from the traditional Chinese herb Rabdosia rubescens (Hemsl.) H. Hara, has demonstrated potent anti-tumor activity in breast Cancer. However, the precise mechanisms of action remain largely unexplored. In this study, we identified Lasiokaurin (LAS) as a novel Autophagy modulator that induces breast Cancer cell death both in vitro and in vivo by dysregulating autophagic flux. Mechanistically, LAS enhances Autophagy initiation but disrupts autophagosome degradation by impairing lysosomal activity through a PDPK1-AKT/mTOR axis. This inhibition of autophagic flux reduces intracellular catabolism and nutrient recycling, leading to metabolic stress in tumor cells. Furthermore, LAS impairs ATP production from glycolysis, ultimately resulting in energy depletion and Cancer cell death. These findings highlight the potential of LAS as an autophagy-targeting therapeutic agent for breast Cancer treatment and provide new insights into its anti-cancer mechanisms.

Keywords

AKT/mTOR; Autophagy; Breast cancer; Glycolysis; Lasiokaurin; PDPK1.

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