Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3

Gu, Y, Chen, M, May, B, Liao, X, Liu, J, Tao, L, Sze, D, Zhang, T and Mo, S 2018, 'Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3', Phytomedicine, vol. 51, pp. 214-225.


Document type: Journal Article
Collection: Journal Articles

Title Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3
Author(s) Gu, Y
Chen, M
May, B
Liao, X
Liu, J
Tao, L
Sze, D
Zhang, T
Mo, S
Year 2018
Journal name Phytomedicine
Volume number 51
Start page 214
End page 225
Total pages 12
Publisher Elsevier GmbH - Urban und Fischer
Abstract Background: The World Health Organization (WHO) reported that colorectal cancer (CRC) was the third most common cancer in men and the second in women, worldwide. Our previous meta-analysis found Sophora flavescens increased tumour response rate in randomised controlled trials of CRC. We hypothesised that its principal constituent matrine had exerted anti-tumour effects. Purpose: To elucidate its mechanisms of action we investigated the dose-related anti-tumour effects of matrine on four human CRC cell-lines: LS174T, Caco-2, SW1116 and RKO. In a LS174T xenografted tumour model in nude mice we assessed the effects of matrine and oxaliplatin on tumour volume, weight and morphology. Computer simulated dockings for target proteins were also conducted. Methods and design: Cell viability, cell cycle and apoptosis were measured by Cell Counting Kit-8 and flow cytometry, and Annexin V-FITC/PI double staining assay respectively. Western blot was performed to examine the expression of Bax, Bcl-2 and caspase-3 in the cells. The xenograft model and immunohistochemistry were used to investigate the effect of matrine in vivo. Oxaliplatin was set as positive control. Molecular docking was performed to predict the binding modes of matrine and oxaliplatin with target proteins using CDOCKER algorithm. Results: Matrine inhibited proliferation of cancer cells in a dose- and time-dependent manner. Matrine induced cell-cycle arrest at G1/G0 phase, induced apoptosis and reduced expression of Bcl-2 and caspase-3 while up-regulating Bax and cleaved caspase-3 in the four CRC cells. In vivo, matrine significantly inhibited tumour growth without side effects on physical health compared to the negative (vehicle) control group. Mice in the oxaliplatin group lost vigour, became frail and lost weight. Expression of Bcl-2 in tumour tissue was lower and Bax expression was higher in the matrine-treated groups compared to the negative control. In computer-simulated docking, matrine successfully docked
Subject Traditional Chinese Medicine and Treatments
Keyword(s) Bcl-2
Caspase-3
Colorectal cancer
Matrine
Molecular docking
Xenograft
DOI - identifier 10.1016/j.phymed.2018.10.004
Copyright notice © 2018 Published by Elsevier GmbH.
ISSN 0944-7113
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 0 times in Scopus Article
Altmetric details:
Access Statistics: 9 Abstract Views  -  Detailed Statistics
Created: Mon, 29 Apr 2019, 13:04:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us