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Mesuaferrea stem bark extract induces apoptosis and inhibits metastasis in human colorectal carcinoma HCT 116 cells, through modulation of multiple cell signalling pathways

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Chinese Journal of Natural Medicines 2017年第7期15卷 505-514页

作者： Muhammad Asif armaghan shafaei Aman Shah Abdul Majid Mohammed Oday Ezzat Saad S Dahham Mohamed B.Khadeer Ahamed Chern Ein Oon Amin Malik Shah Abdul Majid EMAN Testing and Research Laboratory Department of Pharmacology School of Pharmaceutical Sciences Universiti Sains Malaysia Penang 11800 Malaysia Department of Pharmaceutical Chemistry School of Pharmaceutical Sciences Universiti Sains Malaysia Penang 11800 Malaysia Department of Pharmacology School of Medical Sciences Quest International University Perak Malaysia Centre for Drug Research Universiti Sains Malaysia Penang 11800 Malaysia Institute for Research in Molecular Medicine (INFORMM) Universiti Sains Malaysia Penang 11800 Malaysia

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.

关键词： Mesua ferrea a-Amyrin Apoptotic Antimetastatic Molecular pathways

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