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

Abstract

Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results OPEN ACCESSMolecules 2015, 20 18067 suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity.

Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

“…Specifically, we investigated plant sap-derived EVs from four endemic plants collected from Bogildo and Hekseongsan in Korea: Dendropanax Morbifera (DM), Pinus densiflora (PD), Thuja occidentalis (TO), and Chamaecyparis obtusa (CO). It is known that DM and PD extracts have anticancer, antioxidant, antidiabetic, and anti-inflammatory activities, anti-melanogenic effects [25][26][27][28][29][30][31][32][33][34], whereas TO and CO extracts have antioxidant, anti-inflammatory, antimicrobial, and anti-asthmatic effects [35][36][37][38]. EVs isolated from these four kinds of plant saps were investigated for their anticancer effects on normal, low metastatic, and malignant cells.…”

Celastrol Suppresses Tryptophan Catabolism in Human Colon Cancer Cells as Revealed by Metabolic Profiling and Targeted Metabolite Analysis

“…3000000. 10) After culturing for 24h, celastrol (2 and 3 µM) and positive control drug (38.44 µM) were added into the dish for 24h, respectively. After overnight incubation, the medium was removed and the cells were rapidly washed twice with 2 mL PBS, then 1 mL 50% cold methanol (−80°C) was added into the dish for cell quenching and metabolite extraction.…”

“…On HCT116 human colorectal cancer cell line, anti-proliferative activities of Chamaecyparis obtusa (CO) leaf extract was revealed, where the activation of c-Jun N-terminal kinases was found to play a key role 11) ; another cell metabolomics study discovered some important metabolic pathways in the anti-tumor effect of flexibilide, a marine natural compound. 10) In our previous work, celastrol was found to intervene the energy, amino acid and nucleic acid metabolism in human cervical cancer cells. 12) In this study, the cytotoxic effects of celastrol against HCT116 colon cancer cells were investigated and the potential mechanisms were elucidated using metabolic profiling together with targeted metabolite analysis.…”

“…By characterizing the endogenous metabolites in biological systems using liquid chromatography-tandem mass spectrometry (LC-MS) or GC-MS, metabolomics can be used to monitor the metabolic alterations in the intervened pathways in tumor. 10,11) Compared with normal cells, cancer cells have high enzyme activities and high energy metabolism, 12) resulting in specific metabolic characteristics. For example, cancer cell metabolism is more dependent on glucose aerobic glycolysis, which is known as the "Warburg effect."…”

Application of Metabolomics in the Study of Natural Products

“… Disrupt amino acid and fatty acid metabolism [ 17 , 62 ] Activity Schisandrol B Schisandra sphenanthera Schisandrol B protects lithocholic acid-induced cholestasis [ 63 ] Osthole Cnidium moonieri (L.) Cussion/ Angelica pubescens Lipid-lowering potential [ 5 ] Dehydrodiisoeugenol Myristica fragrans Houtt. Anti-bacterial potential [ 15 ] Oxyphylla A Alpinia oxyphylla Oxyphylla A protects neurotoxicity in vitro and in vivo [ 64 ] Berberine Rhizoma Coptidis The anti-diabetic effect of berberine [ 65 , 66 ] Anthricin Chameacyparis obtusa Anthricin protects against human colorectal cancer cell line [ 67 ] Fenugreek Galactomannan Trigonella foenum - graecum L. Fenugreek galactomannan protects diabetic hyperglycemia [ 68 ] Glaucocalyxin A Rabdosia japonica. Glaucocalyxin A has antitumor activity [ 69 ] Gypenoside Gynostemma pentaphyllum (Thunb.)…”