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Selective cytotoxicity of Gomortega keule essential oil through a ROS-mediated pro-apoptotic mechanism
Alejandro Madrid1,2, Valentina Silva1, Alessandra Russo3
1Laboratorio de Productos Naturales y Síntesis Orgánica (LPNSO), Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Valparaíso, Chile.
Abstract:
Cancer is a leading cause of mortality worldwide, prioritizing the search for new therapies with improved toxicity profiles. Natural products, such as essential oils (EOs), are a valuable source of potential chemotherapeutic agents. Gomortega keule, a Chilean endemic tree, has traditional uses, but its cytotoxic potential remains unexplored. This study investigated the chemical composition and cytotoxic activity of Gomortega keule leaf EO. The chemical analysis revealed a unique profile rich in diterpenes (>50%), mainly phyllocladene (28.08%) and kaur-16-ene (19.74%), suggesting a distinct chemotype. The EO demonstrated potent cytotoxic activity against breast (MCF-7), prostate (PC-3), and colon (HT-29) cancer cell lines, with IC50 values of 3.97, 2.43, and 9.76 μg/mL, respectively. Remarkably, the EO exhibited exceptional selectivity, proving significantly more toxic to cancer cells than to non-tumorigenic cells. Specifically, it achieved a Selectivity Index (SI) of 24.01 for breast cancer cells compared to normal MCF-10A cells. Crucially, this selectivity profile significantly outperformed standard chemotherapeutic agents (daunorubicin and 5-fluorouracil), which displayed high toxicity towards healthy cells in this model. The mechanism of action involves the selective induction of reactive oxygen species (ROS), leading to mitochondrial membrane depolarization (ΔΨm) and caspase activation, culminating in apoptotic cell death. These findings highlight G. keule EO as a promising source for developing selective cytotoxic agents.
Insights
Gomortega keule essential oil shows potent and selective anticancer activity against breast, prostate, and colon cancer cells. This natural product induces apoptosis, offering a promising alternative to conventional chemotherapy.
Area of Science:
- Phytochemistry
- Pharmacology
- Cancer Biology
Background:
- Cancer remains a leading global cause of death, driving the need for novel therapies.
- Natural products, including essential oils (EOs), are a rich source of potential anticancer agents.
- The cytotoxic potential of *Gomortega keule*, a Chilean endemic tree, is largely unexplored.
Purpose of the Study:
- To investigate the chemical composition of *Gomortega keule* leaf EO.
- To evaluate the cytotoxic activity and selectivity of *G. keule* EO against various cancer cell lines.
- To elucidate the mechanism of action underlying the EO's anticancer effects.
Main Methods:
- Gas chromatography-mass spectrometry (GC-MS) for chemical profiling.
- In vitro cytotoxicity assays using breast (MCF-7), prostate (PC-3), and colon (HT-29) cancer cell lines, and normal MCF-10A cells.
- Measurement of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and caspase activation to determine the mechanism of action.
Main Results:
- The *G. keule* EO exhibited a unique diterpene-rich profile, with phyllocladene and kaur-16-ene as major components.
- The EO demonstrated potent cytotoxic activity against MCF-7, PC-3, and HT-29 cancer cells (IC50 values: 3.97, 2.43, and 9.76 μg/mL, respectively).
- Remarkably, the EO showed high selectivity for cancer cells over normal cells (Selectivity Index of 24.01 for breast cancer), outperforming standard chemotherapeutics.
Conclusions:
- *Gomortega keule* EO possesses significant cytotoxic and selective anticancer properties.
- The EO selectively induces apoptosis in cancer cells via ROS generation, mitochondrial dysfunction, and caspase activation.
- *G. keule* EO represents a promising natural source for developing novel, selective anticancer agents.
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