Ovatifolin Purified from Leptocarpha rivularis Induces Cell Death in A375 and A2058 Melanoma Cancer Cells
Viviana Burgos1, Nicole Cortez2, Rocío Aguilera-Paillán2
1Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Temuco 4780000, Chile.
Abstract:
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.
Insights
Ovatifolin, isolated from the Chilean plant Leptocarpha rivularis, shows significant cytotoxic and anti-proliferative effects against melanoma cells. This natural compound increases reactive oxygen species and induces apoptosis, offering potential for new skin cancer treatments.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Pharmacology
Background:
- Skin cancer, particularly melanoma, is a growing global health concern with high mortality.
- Drug resistance limits current melanoma therapies, necessitating novel therapeutic strategies.
- Leptocarpha rivularis (Palo negro) is a Chilean plant traditionally used for medicinal purposes, known to produce bioactive compounds.
Purpose of the Study:
- To isolate and identify ovatifolin from L. rivularis.
- To evaluate the antiproliferative and cytotoxic effects of ovatifolin on melanoma cell lines.
- To elucidate the mechanisms underlying ovatifolin's cytotoxic activity.
Main Methods:
- Isolation and structural identification of ovatifolin using NMR and X-ray diffraction.
- Assessment of antiproliferative activity via IncuCyte live-cell analysis and clonogenic assays.
- Evaluation of apoptosis induction using Annexin V staining and caspase inhibition.
Main Results:
- Ovatifolin was successfully isolated and identified from L. rivularis.
- Ovatifolin demonstrated significant cytotoxic activity against A2058 and A375 melanoma cell lines (IC50 values provided).
- Ovatifolin inhibited colony formation, increased intracellular ROS, decreased mitochondrial membrane potential, and induced apoptosis.
Conclusions:
- Ovatifolin is a bioactive compound from L. rivularis with potent antiproliferative and cytotoxic effects on melanoma cells.
- The cytotoxic mechanism involves increased ROS, mitochondrial dysfunction, and apoptosis.
- Ovatifolin represents a promising natural compound for the development of novel melanoma therapies.
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...