Antioxidants, Vol. 14, Pages 1392: Ovatifolin Isolated from Leptocarpha rivularis Induces the Death of A375 and A2958 Cells in Breast Cancer

Antioxidants doi: 10.3390/antiox14121392

Authors:
Viviana Burgos
Nicole Cortez
Rocío Aguilera-Paillán
Sofía Bravo-Bouchat
Bernd Schmidt
Eric Sperlich
Rebeca Pérez
Nelia M. Rodriguez
Leandro Ortiz
Jaime R. Cabrera-Pardo
Cecilia Villegas
Cristian Paz

Skin cancer is increasing worldwide, with melanoma being its most aggressive and lethal form due to its high metastatic potential. Despite therapeutic advances, drug resistance remains a challenge, highlighting the need to explore new anticancer agents. Leptocarpha rivularis is a native plant of Chile, locally called “Palo negro”, and is traditionally used in medicine by the Mapuche people. L. rivularis produces bioactive germacrene sesquiterpenoids with cytotoxic, antioxidant, anti-inflammatory and anti-angiogenic properties. This study reports for the first time the isolation of ovatifolin from aerial parts of L. rivularis and its identification by NMR and X-ray diffraction, together with its antiproliferative activity against two melanoma cell lines. The results show that ovatifolin has cytotoxic activity against the cell lines A2058 and A375, with an IC50 of 27.6 (90.2 µM) and 18.4 µg/mL (60.1 µM), respectively, evaluated by live-cell IncuCyte® analysis. Moreover, ovatifolin arrests colony formation in a clonogenic assay, with an IC50 of 3.26 (10.6 μM) and 3.65 µg/mL (11.9 μM) in these same cell lines. Therefore, ovatifolin increased intracellular ROS and decreased the mitochondrial membrane potential (ΔΨ m). Cell death studies using Annexin V showed that its cytotoxic activity is partially caused by non-specific apoptosis, which was corroborated by the caspase inhibitor Z-VAD with an incomplete recovery of the cell death process.

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