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Updated: Mar 17, 2026
Assessment of Mitochondrial Health in Cancer-Associated Fibroblasts Isolated from 3D Multicellular Lung Tumor Spheroids
Published on: October 21, 2022
Arenobufagin suppresses lung cancer cell growth by disrupting mitochondrial function and inducing relocalization of
Yinglu Yan1, Xiaoling Zhou2, Mingzhen Gu3
1The 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.
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.
Insights
Arenobufagin, a natural compound, effectively inhibits lung cancer cell growth and triggers cell death by disrupting mitochondrial function. It targets ATP synthase, altering cellular energy production and release.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Lung cancer exhibits high global incidence and mortality rates.
- Arenobufagin, a bufadienolide, shows potential anti-tumor properties and inhibits Na+/K+-ATPase.
- Understanding arenobufagin's mechanism in lung cancer is crucial.
Purpose of the Study:
- To investigate the effects of arenobufagin on lung cancer cell proliferation and apoptosis.
- To elucidate the underlying molecular mechanisms of arenobufagin's anti-cancer activity.
- To identify specific cellular targets of arenobufagin in lung cancer.
Main Methods:
- Cell proliferation and colony formation assays were performed.
- Apoptosis induction was assessed.
- Mitochondrial membrane potential and function were analyzed.
- Mass spectrometry identified ATP synthase as a target.
- ATP synthase localization was studied using various techniques.
Main Results:
- Arenobufagin inhibited lung cancer cell proliferation and colony formation at nanomolar concentrations.
- Arenobufagin induced apoptosis by disrupting mitochondrial membrane potential and function.
- ATP synthase was identified as a direct target of arenobufagin.
- Arenobufagin promoted ATP synthase translocation from mitochondria to the plasma membrane.
- This translocation correlated with reduced intracellular ATP and increased extracellular ATP release.
Conclusions:
- Arenobufagin exhibits potent anti-lung cancer effects by inducing apoptosis and inhibiting proliferation.
- Arenobufagin targets ATP synthase, modulating cancer cell energy metabolism.
- The compound disrupts mitochondrial function and alters ATP synthase localization, offering a novel therapeutic strategy.
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