Chamaecyparis lawsoniana Leaf Essential Oil as a Potential Anticancer Agent: Experimental and Computational Studies

Cancer remains one of the leading causes of death worldwide, affected by several factors including oxidative stress; and although conventional synthetic medicines have been used to treat cancer, they often result in various side effects. Consequently, there is a growing need for newer, safer and more effective alternatives, such as natural plant products. Essential oils (EOs) are one such alternative, offering a wide range of bioactivities, including antibacterial, antiviral, antioxidant, and anticancer properties. Accordingly, the objective of the present study was to investigate the chemical composition, as well as the antioxidant and anticancer properties of the leaf essential oil of Chamaecyparis lawsoniana (CLLEO) belonging to the Cupressaceae family. Totally, 59 constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. cis-Abienol, trans-ferruginol, α-cadinol, δ-muurolene and α-pinene were the major components. The in vitro cytotoxicity study against human breast (MCF-7), colon (HCT-116), lung (A-549), hepatocellular (HepG-2) carcinoma cells using MTT assay indicated a promising cytotoxic activity against all the tested cancer cells, particularly HepG-2, with significant selectivity indices. CLLEO exhibited weak antioxidant activity according to the DPPH, ABTS and FRAP assays. In silico docking of these constituents against the epidermal growth factor receptor (EGFR), the myeloid cell leukemia-1 (Mcl-1) and caspase-8 using Molecular Operating Environment (MOE) software demonstrated good binding affinities of the components with the active site of these targets. These findings suggested using CLLEO, or its individual components, as a potentially viable therapeutic option for managing cancerous conditions.

[1]  J. Conway,et al.  A rare isocyanide derived from an unprecedented neutral yttrium(ii) bis(amide) complex , 2023, Chemical science.

[2]  M. Kačániová,et al.  Biological Activity of Cupressus sempervirens Essential Oil , 2023, Plants.

[3]  G. Elnagar,et al.  Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract. , 2023, Journal of ethnopharmacology.

[4]  M. Shariati,et al.  Essential Oils Composition and Biological Activity of Chamaecyparis obtusa, Chrysopogon nigritanus and Lavandula coronopifolia Grown Wild in Sudan , 2023, Molecules.

[5]  M. Mohamed,et al.  Agathis robusta Bark Extract Protects from Renal Ischemia-Reperfusion Injury: Phytochemical, In Silico and In Vivo Studies , 2022, Pharmaceuticals.

[6]  Mona El-Neketi,et al.  Cytotoxic effects of extracts obtained from plants of the Oleaceae family: bio-guided isolation and molecular docking of new secoiridoids from Jasminum humile , 2022, Pharmaceutical biology.

[7]  Y. Antonius,et al.  In-silico screening of inhibitor on protein epidermal growth factor receptor (EGFR) , 2022, IOP Conference Series: Earth and Environmental Science.

[8]  Manmohan Sharma,et al.  A Review on Phytochemical Pharmacological and Biological Activities of Thuja Occidentalis , 2022, Asian Journal of Pharmaceutical Research and Development.

[9]  V. Tešević,et al.  Bioactivity of Chamaecyparis lawsoniana (A. Murray) Parl. and Thuja plicata Donn ex D. Don essential oils on Lymantria dispar (Linnaeus, 1758) (Lepidoptera: Erebidae) larvae and Phytophthora de Bary 1876 root pathogens , 2022, Industrial Crops and Products.

[10]  Y. Bustanji,et al.  Chemical Composition and Antiproliferative and Antioxidant Activities of Essential Oil from Juniperus phoenicea L. Cupressaceae , 2022, Research Journal of Pharmacy and Technology.

[11]  G. Bonanomi,et al.  Persicaria lapathifolia Essential Oil: Chemical Constituents, Antioxidant Activity, and Allelopathic Effect on the Weed Echinochloa colona , 2021, Plants.

[12]  L. Eriksson,et al.  The stressosome, a caspase‐8‐activating signalling complex assembled in response to cell stress in an ATG5‐mediated manner , 2021, Journal of cellular and molecular medicine.

[13]  I. Camele,et al.  Chemical Composition and Antimicrobial Properties of Mentha × piperita cv. ‘Kristinka’ Essential Oil , 2021, Plants.

[14]  S. Ghanbarzadeh,et al.  Green synthesis of silver nanoparticles from Stachys byzantina K. Koch: characterization, antioxidant, antibacterial, and cytotoxic activity , 2021, Particulate Science and Technology.

[15]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[16]  G. Flamini,et al.  Chemical Composition and Cytotoxic Activity of the Fractionated Trunk Bark Essential Oil from Tetraclinis articulata (Vahl) Mast. Growing in Tunisia , 2021, Molecules.

[17]  M. K. Abd El-Rahman,et al.  Antioxidant, anti-inflammatory and cytotoxic activities of the unsaponifiable fraction of extra virgin olive oil , 2020, Grasas y Aceites.

[18]  Arvind Negi,et al.  Development of Mcl-1 inhibitors for cancer therapy. , 2020, European journal of medicinal chemistry.

[19]  V. De Feo,et al.  Biological investigations of essential oils extracted from three Juniperus species and evaluation of their antimicrobial, antioxidant and cytotoxic activities , 2020, Journal of applied microbiology.

[20]  I. Borovik,et al.  Antibacterial and fungicidal effect of ethanol extracts from Juniperus sabina, Chamaecyparis lawsoniana, Pseudotsuga menziesii and Cephalotaxus harringtonia , 2020 .

[21]  M. Mohamed,et al.  Essential Oil from Myrtle Leaves Growing in the Eastern Part of Saudi Arabia: Components, Anti-inflammatory and Cytotoxic Activities , 2019, Journal of Essential Oil Bearing Plants.

[22]  C. Méndez-Cuesta,et al.  Cytotoxic Activity of Essential Oils of Some Species from Lamiaceae Family , 2019, Cytotoxicity - Definition, Identification, and Cytotoxic Compounds.

[23]  T. Akbarzadeh,et al.  Cytotoxic Activity of Juniperus excelsa M. Bieb. Leaves Essential Oil in Breast Cancer Cell Lines , 2019 .

[24]  A. Hassani,et al.  Essential oil composition and antimicrobial activities of some Cupressaceae species from Algeria against two phytopathogenic microorganisms , 2019 .

[25]  L. Craker,et al.  Role of Medicinal and Aromatic Plants: Past, Present, and Future , 2019, Pharmacognosy - Medicinal Plants.

[26]  B. Kumar,et al.  Promising Targets in Anti-cancer Drug Development: Recent Updates. , 2018, Current medicinal chemistry.

[27]  F. Tomi,et al.  Chemical composition of the leaf oil of Artabotrys jollyanus from Côte d’Ivoire , 2017 .

[28]  P. Wee,et al.  Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways , 2017, Cancers.

[29]  Eman Ramadan Elsharkawy,et al.  Comparative Study of Antioxidant and Anticancer Activity of Thuja orientalis Growing in Egypt and Saudi Arabia , 2017 .

[30]  M. Sharifi-Rad,et al.  Biological Activities of Essential Oils: From Plant Chemoecology to Traditional Healing Systems , 2017, Molecules.

[31]  L. Barbosa,et al.  Chemical Variability and Biological Activities of Eucalyptus spp. Essential Oils , 2016, Molecules.

[32]  M. Elaasser,et al.  Synthesis and anticancer activity of arylazothiazoles and 1,3,4-thiadiazoles using chitosan-grafted-poly(4-vinylpyridine) as a novel copolymer basic catalyst , 2015, Chemistry of Heterocyclic Compounds.

[33]  Sayed A. Fayed Chemical Composition, Antioxidant, Anticancer Properties and Toxicity Evaluation of Leaf Essential Oil of Cupressus sempervirens , 2015 .

[34]  Young-S. Kim,et al.  Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics , 2015, Molecules.

[35]  A. Cherif,et al.  Chemical Composition, Antioxidant Potential, and Antibacterial Activity of Essential Oil Cones of Tunisian Cupressus sempervirens , 2015 .

[36]  A. Matsuo,et al.  Chemical Composition and in vitro Cytotoxic and Antileishmanial Activities of Extract and Essential Oil from Leaves of Piper cernuum , 2015, Natural product communications.

[37]  Sunil Kumar,et al.  Pharmacognostic study of Chamaecyparis lawsoniana (Murr.) Parl.: A drug used in Homoeopathy , 2015 .

[38]  G. Zeng,et al.  Sesquiterpenoids and Diterpenes from Chamaecyparis obtusa var. breviramea f. crippsii. , 2014 .

[39]  G. Zeng,et al.  Sesquiterpenoids and Diterpenes from Chamaecyparis obtusa var. breviramea f. crippsii , 2014 .

[40]  Kaleigh Fernald,et al.  Evading apoptosis in cancer. , 2013, Trends in cell biology.

[41]  D. Papachristos,et al.  Essential oil composition, adult repellency and larvicidal activity of eight Cupressaceae species from Greece against Aedes albopictus (Diptera: Culicidae) , 2013, Parasitology Research.

[42]  Lin Xiao,et al.  A New Phenolic Glycoside from Chamaecyparis obtusa var. breviramea f. crippsii , 2013, Molecules.

[43]  A. Soria,et al.  Antifungal and Antibacterial Activity of the Essential Oil of Chamaecyparis Lawsoniana from Spain , 2012, Natural product communications.

[44]  Rebecca SY Wong,et al.  Apoptosis in cancer: from pathogenesis to treatment , 2011, Journal of experimental & clinical cancer research : CR.

[45]  K. Gwak,et al.  Whitening and Antioxidant Activities of Essential Oils from Cryptomeria japonica and Chamaecyparis obtusa , 2011 .

[46]  J. Casanova,et al.  Combined Analysis by GC (RI), GC-MS and 13C NMR of the Supercritical Fluid Extract of Abies alba Twigs , 2010, Natural product communications.

[47]  M. Miguel Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review , 2010, Molecules.

[48]  X. Fernandez,et al.  Chemical composition and antimicrobial activity of essential oils isolated from Algerian Juniperus phoenicea L. and Cupressus sempervirens L. , 2010 .

[49]  Chen Kaiyun,et al.  Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo. , 2010, Surgery.

[50]  U. Palanisamy,et al.  Standardised Mangifera indica extract is an ideal antioxidant , 2009 .

[51]  J. Asili,et al.  Identification of Volatile Oil Components from Aerial Parts of Chamaecyparis lawsoniana by GC-MS and 13C-NMR Methods , 2009 .

[52]  Lien Ai Pham-Huy,et al.  Free Radicals, Antioxidants in Disease and Health , 2008, International journal of biomedical science : IJBS.

[53]  B. Li,et al.  Inducing apoptosis and enhancing chemosensitivity to Gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell , 2008, Cancer Chemotherapy and Pharmacology.

[54]  P. Lech,et al.  Gas chromatographic–mass spectrometric investigation of metabolites from the needles and roots of pine seedlings at early stages of pathogenic fungi Armillaria ostoyae attack , 2008, Trees.

[55]  Erinna F. Lee,et al.  Structural insights into the degradation of Mcl-1 induced by BH3 domains , 2007, Proceedings of the National Academy of Sciences.

[56]  R. Adams,et al.  Identification of Essential Oil Components By Gas Chromatography/Mass Spectrometry , 2007 .

[57]  S. Fulda,et al.  Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy , 2006, Oncogene.

[58]  C. Hse,et al.  Antioxidant activity of extracts from the bark of Chamaecyparis lawsoniana (A. Murray) Parl. , 2006 .

[59]  A. Yaşar,et al.  GC-MS Analysis of Chloroform Extracts in Flowers, Stems, and Roots of Tripleurospermum callosum. , 2005 .

[60]  A. Medici,et al.  Composition and functional properties of the essential oil of amazonian basil, Ocimum micranthum Willd., Labiatae in comparison with commercial essential oils. , 2004, Journal of agricultural and food chemistry.

[61]  M. Sliwkowski,et al.  Structure of the Epidermal Growth Factor Receptor Kinase Domain Alone and in Complex with a 4-Anilinoquinazoline Inhibitor* , 2002, The Journal of Biological Chemistry.

[62]  W. König,et al.  epi-Cubebanes from Solidago canadensis. , 2002, Phytochemistry.

[63]  M. Grütter,et al.  Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex. , 2000, Journal of molecular biology.

[64]  E. Stashenko,et al.  HRGC/FID and HRGC/MSD analysis of the secondary metabolites obtained by different extraction methods from Lepechinia schiedeana, and in vitro evaluation of its antioxidant activity , 1999 .

[65]  L. Nahar,et al.  Anticancer natural products , 2020 .

[66]  Ching-Dong Chang,et al.  Antioxidant Activities and Oral Toxicity Studies of Chamaecyparis formosensis and Cymbopogon nardus Essential Oils , 2016 .

[67]  V. Rani,et al.  Free Radicals in Human Health and Disease , 2015, Springer India.

[68]  Shalini Mani Production of Reactive Oxygen Species and Its Implication in Human Diseases , 2015 .

[69]  G. Buchbauer,et al.  A review on recent research results (2008–2010) on essential oils as antimicrobials and antifungals. A review. , 2012 .

[70]  G. Kaatz,et al.  Antibacterials and modulators of bacterial resistance from the immature cones of Chamaecyparis lawsoniana. , 2007, Phytochemistry.

[71]  C. Hse,et al.  Article in press-uncorrected proof Antioxidant activity of extracts from the bark of Chamaecyparis lawsoniana ( A . Murray ) , 2006 .

[72]  Scott C Frost,et al.  Essential oil composition of four Lomatium Raf. species and their chemotaxonomy , 2005 .

[73]  A. Šmelcerović,et al.  Chemical constituents and antimicrobial activity of the ethanol extracts obtained from the flower, leaf and stem of Salvia officinalis L. , 2003 .

[74]  J. Vermeesch,et al.  Volatile Fractions of Chamaecyparis lawsoniana (A. Murray) Parl, and Chamaecyparis pisifera (Sieb. et Zucc.) Endl. var. filifera. Identification of Oplopanonyl Acetate , 1991 .