Papuamine Inhibits Viability of Non-small Cell Lung Cancer Cells by Inducing Mitochondrial Dysfunction
Hye-Young Min1, Yujin Jung2, Kwan Hee Park3
1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Background/Aim:
Despite the Warburg effect, mitochondria play an essential role in the survival and maintenance of cancer cells. Thus, mitochondria have been considered a target for anticancer agents. Here, we identified a mitochondria-targeting anticancer agent from natural products.
Materials And Methods:
Morphological and functional changes in mitochondria were determined by a fluorescence-based High Content Imaging System. Using human non-small cell lung cancer (NSCLC) cell lines (H1299, H226B, and A549), cell viability and colony formation assays, cell cycle analysis, and immunoblotting were performed to determine cytotoxic and proapoptotic effects of papuamine.
Results:
Using a natural product chemical library, we identified papuamine as an active compound to inhibit viability and ATP production of NSCLC cells. Papuamine depleted intracellular ATP by causing mitochondrial dysfunction, as indicated by the loss of the mitochondrial membrane potential and increased mitochondrial superoxide generation. Papuamine significantly inhibited viability and colony formation of NSCLC cells by inducing apoptosis.
Conclusion:
Papuamine has a potential as a novel mitochondria-targeting anticancer agent.
Insights
Papuamine, a natural product, effectively targets cancer cell mitochondria, inhibiting their viability and ATP production. This compound shows promise as a novel anticancer agent by inducing apoptosis in non-small cell lung cancer cells.
Area of Science:
- Mitochondrial biology
- Cancer research
- Natural product chemistry
Background:
- Mitochondria are crucial for cancer cell survival, even with the Warburg effect.
- Mitochondria represent a viable target for developing novel anticancer agents.
Purpose of the Study:
- Identify a mitochondria-targeting anticancer agent from natural products.
- Evaluate the efficacy of papuamine against non-small cell lung cancer (NSCLC).
Main Methods:
- High Content Imaging System for mitochondrial analysis.
- Cell viability, colony formation, cell cycle, and immunoblotting assays.
- Utilized NSCLC cell lines (H1299, H226B, A549).
Main Results:
- Papuamine inhibited NSCLC cell viability and ATP production.
- Papuamine induced mitochondrial dysfunction, including loss of membrane potential and increased superoxide generation.
- Papuamine significantly inhibited colony formation and induced apoptosis in NSCLC cells.
Conclusions:
- Papuamine demonstrates potential as a novel anticancer agent.
- Papuamine's mechanism involves targeting cancer cell mitochondria.
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