2. Academic Validation
  3. Arenobufagin suppresses lung cancer cell growth by disrupting mitochondrial function and inducing relocalization of ATP synthase

Arenobufagin suppresses lung cancer cell growth by disrupting mitochondrial function and inducing relocalization of ATP synthase

  • Toxicon. 2026 Jun 15:276:109067. doi: 10.1016/j.toxicon.2026.109067.
Yinglu Yan 1,  Xiaoling Zhou 2,  Mingzhen Gu 3,  Yanyu Ding 2,  Xinlin Zhao 2,  Zhiying Zhou 2,  Jiyuan Ke 4
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, 4090 Susong Rd, Hefei, Anhui, 230601, China.
  • 2 Institute of Health and Medicine, Hefei Comprehensive National Science Center, 4090 Susong Rd, Hefei, Anhui, 230601, China; Department of Immunology, School of Basic Medical Sciences, Center for Big Data and Population Health of Institute of Health and Medicine (IHM), Anhui Medical University, Hefei, 230032, China.
  • 3 Institute of Health and Medicine, Hefei Comprehensive National Science Center, 4090 Susong Rd, Hefei, Anhui, 230601, China.
  • 4 The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, 4090 Susong Rd, Hefei, Anhui, 230601, China; Department of Immunology, School of Basic Medical Sciences, Center for Big Data and Population Health of Institute of Health and Medicine (IHM), Anhui Medical University, Hefei, 230032, China. Electronic address: [email protected].
PMID: 41833738 DOI: 10.1016/j.toxicon.2026.109067
Abstract

Lung Cancer has the highest incidence and mortality rates among all cancers worldwide. Arenobufagin, a steroidal lactone of the bufadienolide class, has been reported to possess anti-tumor activity and to inhibit Na+/K+-ATPase. In this study, we investigated the effects of arenobufagin on lung Cancer cell growth and its underlying mechanisms. We found that arenobufagin inhibits lung Cancer cell proliferation and colony formation, and induces Apoptosis at nanomolar concentrations. Mechanistically, arenobufagin disrupts mitochondrial membrane potential and function, thereby triggering Apoptosis. Mass spectrometry analysis further identified ATP Synthase as a cellular target of arenobufagin. Notably, arenobufagin treatment promotes the translocation of ATP Synthase from mitochondria to the plasma membrane, a process associated with reduced intracellular ATP production and increased extracellular ATP release. Collectively, our findings establish arenobufagin as a regulator of Cancer cell energy metabolism by modulating ATP Synthase localization and mitochondrial function.

Keywords

ATP synthase; Arenobufagin; Bufadienolide; Chansu; Lung cancer; Mitochondrial membrane potential; Toad venom; Traditional Chinese medicine.

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