Insight into Analysis of Essential Oil from Anisosciadium lanatum Boiss.-Chemical Composition, Molecular Docking, and Mitigation of Hepg2 Cancer Cells through Apoptotic Markers.

Hossam M. Darrag,Hairul-Islam Mohamed Ibrahim,Hany Ezzat Khalil,Katsuyoshi Matsunami

doi:10.3390/plants11010066

Abstract

Essential oils have been used in various traditional healing systems since ancient times worldwide, due to their diverse biological activities. Several studies have demonstrated their plethora of biological activities—including anti-cancer activity—in a number of cell lines. Anisosciadium lanatum Boiss. is a perennial aromatic herb. Traditionally, it is an edible safe herb with few studies exploring its importance. The current study aims to investigate the chemical composition of essential oil isolated from Anisosciadium lanatum using GC-MS, as well as report its anti-cancer potential and its mechanistic effect on HepG2 liver cancer cell lines, and conduct molecular docking studies. To achieve this, the essential oil was isolated using a Clevenger apparatus and analyzed using GC-MS. The cell viability of HepG2 liver cancer and normal fibroblast NIH-3T3 cell lines was assessed by MTT cytotoxicity assay. The effects of the essential oil on cell migration and invasion were assessed using wound healing and matrigel assays, respectively. The effect of the essential oil on migration and apoptotic-regulating mRNA and proteins was quantified using quantitative real-time PCR and Western blot techniques, respectively. Finally, computational docking tools were used to analyze in silico binding of major constituents from the essential oil against apoptotic and migration markers. A total of 38 components were identified and quantified. The essential oil demonstrated regulation of cell proliferation and cell viability in HepG2 liver cancer cells at a sub-lethal dose of 10 to 25 μg/mL, and expressed reductions of migration and invasion. The treatment with essential oil indicated mitigation of cancer activity by aborting the mRNA of pro-apoptotic markers such as BCL-2, CASPASE-3, CYP-1A1, and NFκB. The algorithm-based binding studies demonstrated that eucalyptol, nerol, camphor, and linalool have potent binding towards the anti-apoptotic protein BCL-2. On the other hand, camphor and eucalyptol showed potent binding towards the pro-apoptotic protein CASPASE-3. These findings highlight the effectiveness of the essential oil isolated from Anisosciadium lanatum to drive alleviation of HepG2 cancer cell progression by modulating apoptotic markers. Our findings suggest that Anisosciadium lanatum could be used as a phytotherapeutic anti-cancer agent, acting through the regulation of apoptotic markers. More well-designed in vivo trials are needed in order to verify the obtained results.

Highlights

Medicinal and aromatic plants have been considered to play essential roles in the field of therapeutics all over the world [1]
Further molecular modulations showed that EO increased the mRNA of CASPASE-3 expression levels, as well as increased and reciprocally regulated the protein expression levels of BCL-2 and NFκB (Figure 5). These results suggest that EO promoted apoptosis in and inhibited the invasiveness of HepG2 liver cancer cells
Camphor and eucalyptol alone showed significant binding against pro-apoptotic CASPASE-3 regulatory molecules. These findings suggest that the EO from A. lanatum can control hepatoma HepG2 liver cancer cells through the reciprocal regulation of apoptotic markers

Summary

Introduction

Medicinal and aromatic plants have been considered to play essential roles in the field of therapeutics all over the world [1]. Essential oils (Eos), as secondary metabolites produced from such medicinal and aromatic plants, offer great value in terms of their various curative and biological properties. Several investigations have demonstrated the anti-inflammatory, anti-oxidant, anti-fungal, anti-microbial, and cytotoxic activities of such Eos [2,3,4]. More than 75% of anti-cancer drugs are directly or indirectly derived from medicinal plants [5]. In this context, the discovery of new natural product candidates with anticancer properties has unique interest for the purpose of medical care [6]. Food enriched with vitamins and bioactive phytochemicals could act as tumor-controlling agents to reduce cancer progression, especially in the case of liver or colon cancer [9]

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