Natural Product Epipyrone A from Epicoccum nigrum Exhibits Antiproliferative Activity on Canine Mammary Tumor Cells Through PI3K/Akt/mTOR Pathway Modulation

Q: What is Epipyrone A (Epy A) and where does it come from in this study?

Epy A is a fungal pigment first isolated from Epicoccum nigrum and then tested in vitro on canine mammary tumor cell lines.

Q: How does Epy A affect canine mammary tumor cells in vitro?

Epy A significantly reduces cell viability in both P114 and CF33 lines in a concentration- and time-dependent manner, inhibits migration, and in P114 increases total antioxidant capacity while reducing ROS levels.

Q: What molecular pathway does Epy A modulate?

Western blot analysis indicates modulation of the PI3K/Akt/mTOR pathway, with P114 showing decreased mTOR and p-Akt, while CF33 shows increased Akt and p-Akt alongside reduced mTOR, consistent with a compensatory feedback mechanism.

Sep 23, 2026

Uploaded by Theodore

Canine mammary tumors (CMTs) are among the most common neoplasms in female dogs, and therapeutic options remain limited and non-standardized, motivating the search for alternative agents such as fungal secondary metabolites. This study isolates Epipyrone A (Epy A) from Epicoccum nigrum and evaluates it in vitro on two CMT cell lines (P114 and CF33). Epy A reduces viability in a concentration- and time-dependent manner, suppresses migration, enhances antioxidant capacity in P114, and decreases ROS. Western blot results show PI3K/Akt/mTOR pathway modulation, with distinct compensatory patterns between cell lines, supporting Epy A as a promising candidate for innovative veterinary and comparative oncology therapies.

LanguageEnglish

CategoryHealthcare

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Abstract

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1. Introduction

Article Natural Product Epipyrone A from Epicoccum nigrum Exhibits Antiproliferative Activity on Canine Mammary Tumor Cells Through PI3K/Akt/mTOR Pathway Modulation Consiglia Longobardi 1,†, Daria Lotito 1,†, Alessia Staropoli 1, Valeria Iervolino 1, Nunzio Antonio Cacciola 1, Serena Montagnaro 1, Francesco Vinale 1,2, Sara Damiano 1, * and Roberto Ciarcia 1 1 Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; [consiglia.longobardi@unina.it](consiglia.longobardi@unina.it) (C.L.); daria.lotito@unina.it (D.L.); [alessia.staropoli@unina.it](alessia.staropoli@unina.it) (A.S.); [valeria.iervolino@unina.it](valeria.iervolino@unina.it) (V.I.); [nunzioantonio.cacciola@unina.it](nunzioantonio.cacciola@unina.it) (N.A.C.); [serena.montagnaro@unina.it](serena.montagnaro@unina.it) (S.M.); [frvinale@unina.it](frvinale@unina.it) (F.V.); [rciarcia@unina.it](rciarcia@unina.it) (R.C.) 2 Institute for Sustainable Plant Protection, National Research Council, Piazzale E. Fermi, 1, 80055 Portici, Naples, Italy * Correspondence: [sara.damiano@unina.it](sara.damiano@unina.it)[ ](sara.damiano@unina.it)† These authors contributed equally to this work. Academic Editors: José M. Matés and Constantinos Giaginis Received: 16 December 2025 Revised: 20 January 2026 Accepted: 24 January 2026 Published: 28 January 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 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. Keywords: canine mammary tumors; Epipyrone A; Epicoccum nigrum; PI3K/Akt/mTOR pathway 1. Introduction The percentage of cancer-related deaths in companion dogs ranges from 15% to 30%, depending on the country and breed. In developed nations, cancer often emerges asthe primary cause of mortality as life expectancy rises [1] . Because canines and humans live in the same environment and share some genetic features, spontaneous tumours in dogs represent a clinically relevant model of human cancer, as they typically mirror the genetic and biological complexity of human disease, also exhibiting pronounced intra-and inter-patient heterogeneity [2] . Moreover, canine cancers frequently acquire therapeutic resistance and display a strong propensity to metastasize, further reinforcing their translational significance to humans [3,4] . Among these, canine mammary tumours (CMTs) are the most frequently diagnosed in female dogs, second only to skin tumours, and thus represent a significant challenge

FAQs

What is Epipyrone A (Epy A) and where does it come from in this study?

Epy A is a fungal pigment first isolated from Epicoccum nigrum and then tested in vitro on canine mammary tumor cell lines.

How does Epy A affect canine mammary tumor cells in vitro?

Epy A significantly reduces cell viability in both P114 and CF33 lines in a concentration- and time-dependent manner, inhibits migration, and in P114 increases total antioxidant capacity while reducing ROS levels.

What molecular pathway does Epy A modulate?

Western blot analysis indicates modulation of the PI3K/Akt/mTOR pathway, with P114 showing decreased mTOR and p-Akt, while CF33 shows increased Akt and p-Akt alongside reduced mTOR, consistent with a compensatory feedback mechanism.

Sep 23, 2026

Uploaded by Theodore