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Natural Product Epipyrone A from Epicoccum nigrum Exhibits Antiproliferative Activity on Canine Mammary Tumor Cells
Consiglia Longobardi1, Daria Lotito1, Alessia Staropoli1
1Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy.
Abstract:
Canine mammary tumors (CMTs) are among the most frequent neoplasms in female dogs, with current therapeutic options being limited and non-standardized, prompting the search for alternative treatments such as fungal secondary metabolites. In this study, the fungal pigment Epipyrone A (Epy A) was first isolated from Epicoccum nigrum and then tested in vitro on two CMT cell lines, P114 and CF33. The compound significantly reduced cell viability in both lines in a concentration- and time-dependent manner (p < 0.05), with the strongest effect observed at 175 µg/mL after 48 h (p < 0.0001), while showing no cytotoxicity in MDCK non-tumor cells. Epy A also inhibited cell migration and increased total antioxidant capacity in P114 cells, accompanied by a significant reduction in ROS levels. Western blot analysis revealed modulation of the PI3K/Akt/mTOR pathway, crucial in CMT biology. Specifically, P114 cells showed downregulation of mTOR and p-Akt, indicating inhibition of proliferative signaling, whereas CF33 cells exhibited increased Akt and p-Akt alongside reduced mTOR, consistent with a compensatory feedback mechanism, probably linked to the changing in oxidative balance after treatment. Overall, these results identified Epy A as a promising natural molecule with potential applications in innovative therapeutic approaches for veterinary and comparative oncology.
Insights
Epipyrone A, a fungal pigment, effectively reduced canine mammary tumor cell viability and migration in vitro. This natural compound shows promise as a novel therapeutic agent for veterinary oncology.
Area of Science:
- Veterinary Medicine
- Natural Product Chemistry
- Oncology
Background:
- Canine mammary tumors (CMTs) are common in female dogs, with limited treatment options.
- Fungal secondary metabolites are being explored as alternative cancer therapies.
Purpose of the Study:
- To investigate the anti-cancer potential of Epipyrone A (Epy A), a fungal pigment, against canine mammary tumor (CMT) cell lines.
- To evaluate the effects of Epy A on cell viability, migration, oxidative stress, and key signaling pathways in CMTs.
Main Methods:
- Epipyrone A was isolated from *Epicoccum nigrum*.
- In vitro testing on CMT cell lines (P114, CF33) and non-tumor MDCK cells.
- Assays for cell viability, migration, antioxidant capacity, and reactive oxygen species (ROS) levels.
- Western blot analysis to assess the PI3K/Akt/mTOR pathway.
Main Results:
- Epy A significantly reduced CMT cell viability in a dose- and time-dependent manner, with no toxicity to normal cells.
- Epy A inhibited cell migration and increased antioxidant capacity in P114 cells, reducing ROS levels.
- Western blot analysis showed Epy A modulated the PI3K/Akt/mTOR pathway, with different effects on P114 and CF33 cells.
Conclusions:
- Epipyrone A demonstrates significant anti-cancer activity against canine mammary tumor cells in vitro.
- Epy A's mechanism involves modulation of cell proliferation and oxidative balance pathways.
- This fungal pigment represents a promising candidate for developing novel therapeutic strategies in veterinary and comparative oncology.
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