Abstract
Objective:To investigate vetiver oil (VO) selectivity effects on several cancer cell types and identify the β-caryophyllene role and mechanisms to prevent cancer development. Methods:Cytotoxic effects of VO on three types of cancer cells (WiDr, 4T1, T47D) were determined using MTT assay. VO’s effects on the cell cycle and apoptosis were analyzed using flow cytometry. Intracellular Reactive Oxygen Species (ROS) of cells after treatment with VO was observed with DCFDA staining. Bioinformatics study and molecular docking were used to determine the molecular targets of VO. Results:VO contained various essential oils in which β-caryophyllene was the most abundant. 4T1 cells performed the lowest IC50 value. WiDr and 4T1 cells showed an arrest in the G2/M phase, while T47D showed an increase of sub G1 population after VO treatment. On the other hand, apoptosis was only observed in WiDr and T47D cells. ROS levels were increased significantly in WiDr and T47D cells but not in 4T1 cells. Cannabinoids CB2 receptor (CNR2) was highly expressed in 4T1 cells and commonly exhibited a low survival rate on Triple Negative Breast Cancer (TNBC) patients. CNR2 was the notable target of β-caryophyllene and performed agonistic interaction, which might have contributed to its cytotoxic activity against 4T1 cells.Conclusion:The molecular interaction of VO cannabinoid agonists and the CNR2 receptor was the underlying cause of VO cytotoxicity, which is a VO distinction on TNBC. Therefore, VO is better suited for use as an anti-cancer agent in TNBC cells.
Highlights
Cannabinoids receptor (CNR) has been studied as a potential target for treating various diseases, including the progression of cancer and its deteriorating prognosis (Kisková et al, 2019)
Ceramide induces apoptosis by regulating the p38 mitogen-activated protein kinase (MAPK) signaling, while in lung cancer, the ceramide-dependent pro-apoptotic effect appears to be mediated by the up-regulation of COX-2 expression and the increased synthesis of the pro-apoptotic prostaglandin E-2 (PGE-2), which are triggered by cannabinoid agonists (Hinz and Ramer, 2019)
Most of the activities of vetiver oil (VO) were thought to come from the terpenoid group, which was known to have an extensive enough abundance that acts as a biomarker, namely β-caryophyllene (15.43%)
Summary
Cannabinoids receptor (CNR) has been studied as a potential target for treating various diseases, including the progression of cancer and its deteriorating prognosis (Kisková et al, 2019). CNR1 is highly expressed in brain areas, and it is found to be low in the peripheral nervous system, testes, prostate, uterus, and vascular endothelium This receptor is dominant in cognitive function, memory, anxiety, pain, motor regulation, and endocrine regulation (Dhopeshwarkar and Mackie, 2014). The different tissue distributions of CNR1 and CNR2 allow different receptor effects with selective and specific activation pathways Both types of CNR are highly expressed in various cancer tissues, but CNR2 plays a more critical role in carcinogenesis and cancer development (Raup-Konsavage et al, 2018). Several studies have found that when cancer cells are treated with cannabinoid agonists, the PI3K/Akt and MAPK/ ERK signaling pathways are involved in controlling cell proliferation and survival (Khan et al, 2018). Ceramide induces apoptosis by regulating the p38 MAPK signaling, while in lung cancer, the ceramide-dependent pro-apoptotic effect appears to be mediated by the up-regulation of COX-2 expression and the increased synthesis of the pro-apoptotic prostaglandin E-2 (PGE-2), which are triggered by cannabinoid agonists (Hinz and Ramer, 2019)
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