Mesua ferrea stem bark extract induces apoptosis and inhibits metastasis in human colorectal carcinoma HCT 116 cells, through modulation of multiple cell signalling pathways.
10.1016/S1875-5364(17)30076-6
- Author:
Muhammad ASIF
1
;
Armaghan SHAFAEI
2
;
Aman Shah ABDUL MAJID
3
;
Mohammed Oday EZZAT
4
;
Saad S DAHHAM
5
;
Mohamed B Khadeer AHAMED
5
;
Chern Ein OON
6
;
Amin Malik Shah ABDUL MAJID
7
Author Information
1. EMAN Testing and Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia. Electronic address: asif_pharmacist45@yahoo.com.
2. Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
3. Department of Pharmacology, School of Medical Sciences, Quest International University, Perak, Malaysia.
4. Centre for Drug Research, Universiti Sains Malaysia, Penang, 11800, Malaysia.
5. EMAN Testing and Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
6. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia.
7. EMAN Testing and Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia. Electronic address: Aminmalikshah@gmail.com.
- Publication Type:Journal Article
- Keywords:
Antimetastatic;
Apoptotic;
Mesua ferrea;
Molecular pathways;
α-Amyrin
- MeSH:
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Cell Line, Tumor;
Colorectal Neoplasms;
drug therapy;
metabolism;
pathology;
physiopathology;
ErbB Receptors;
genetics;
metabolism;
HCT116 Cells;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit;
genetics;
metabolism;
Magnoliopsida;
chemistry;
Neoplasm Metastasis;
prevention & control;
Plant Bark;
chemistry;
Plant Extracts;
pharmacology;
Signal Transduction;
drug effects;
Wnt Proteins;
genetics;
metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(7):505-514
- CountryChina
- Language:English
-
Abstract:
Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and -3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways.
