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Deciphering the Mechanisms Underlying the Antitumor Effects of Eucalyptus Essential Oil and Its Component
Sonia Ben Hamouda1, Ons Zakraoui1, Sonia Souissi1
1Institut Pasteur de Tunis, LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale, Université de Tunis El Manar, Tunis 1002, Tunisia.
Abstract:
The development of non-toxic, novel anti-tumor alternatives that target key hallmark events of tumor progression is of a high priority for cancer therapy. Natural compounds, such as Essential oils (EOs) derived from plant extracts are a mixture of chemical components known for their diverse pharmacological properties, including anticancer potential. For this purpose, we investigated the antitumor activity of Eucalyptus globulus essential oil (EEO) and its major constituents against colorectal cancer cells in vitro. EEO significantly reduced the viability of colon cancer LS174 cells, induced caspase-dependent apoptosis and triggered cell cycle arrest by modulating the expression of several effectors involved in these processes. Mechanistically, EEO exhibited its activity by targeting p38, SAPK/JNK, ERK1/2, and AKT kinases in LS174 cells. Considering the pivotal role of p53 status in mediating the response to anticancer therapies, we further investigated the effects of Eucalyptol, 3-Cyclohexene-1-methanol, α-Pinene, and α-Terpineol, identified as major components of EEO, on the viability of human colon adenocarcinoma LS174 (wild type p53) and HT29 (mutant p53) cell lines. Interestingly, we highlighted for the first time that 3-Cyclohexene-1-methanol exhibited the most anti-proliferative activity against both tumor cells irrespective to their p53 status. It exerted its effect by inducing apoptotic cell death, disturbing cell cycle progression along with reducing the phosphorylation of key components of the proliferation and survival pathways p38, ERK1/2, and AKT kinases. Our results suggest that Eucalyptus essential oil and its component, 3-Cyclohexene-1-methanol represent promising multi-targeting candidates for colorectal cancer therapy.
Insights
Eucalyptus globulus essential oil (EEO) shows anti-tumor effects against colorectal cancer cells by inducing apoptosis and cell cycle arrest. A key component, 3-Cyclohexene-1-methanol, demonstrates significant anti-proliferative activity, regardless of p53 status.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Pharmacology
Background:
- Non-toxic anti-tumor agents are crucial for cancer therapy.
- Essential oils (EOs) from plant extracts possess diverse pharmacological properties, including anticancer potential.
- Investigating natural compounds offers novel therapeutic strategies for cancer treatment.
Purpose of the Study:
- To evaluate the antitumor activity of Eucalyptus globulus essential oil (EEO) and its constituents against colorectal cancer cells.
- To elucidate the mechanisms underlying EEO's anti-cancer effects, including apoptosis induction and cell cycle modulation.
- To identify specific EEO components with significant anti-proliferative activity, irrespective of p53 status.
Main Methods:
- In vitro assessment of EEO and its major constituents (Eucalyptol, 3-Cyclohexene-1-methanol, α-Pinene, α-Terpineol) on human colon adenocarcinoma cell lines (LS174 and HT29).
- Analysis of cell viability, apoptosis induction (caspase-dependent), and cell cycle progression.
- Investigation of kinase signaling pathways (p38, SAPK/JNK, ERK1/2, AKT) affected by EEO and its components.
Main Results:
- EEO significantly reduced LS174 cell viability, induced apoptosis, and caused cell cycle arrest.
- EEO modulated the expression of key effectors involved in apoptosis and cell cycle regulation.
- 3-Cyclohexene-1-methanol demonstrated the most potent anti-proliferative activity against both LS174 (wild type p53) and HT29 (mutant p53) cells.
- 3-Cyclohexene-1-methanol induced apoptosis, disturbed cell cycle progression, and reduced phosphorylation of p38, ERK1/2, and AKT kinases.
Conclusions:
- Eucalyptus globulus essential oil exhibits significant anti-colorectal cancer activity in vitro.
- The component 3-Cyclohexene-1-methanol is a promising candidate for colorectal cancer therapy due to its potent anti-proliferative effects.
- EEO and its component 3-Cyclohexene-1-methanol act through multi-targeting mechanisms involving apoptosis and cell cycle regulation, offering potential for novel cancer treatments.
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