Induction of G2/M phase arrest and apoptosis by a new tetrahydroingenol diterpenoid from Euphorbia erythradenia Bioss. in melanoma cancer cells

(2017) Induction of G2/M phase arrest and apoptosis by a new tetrahydroingenol diterpenoid from Euphorbia erythradenia Bioss. in melanoma cancer cells. Biomedicine & Pharmacotherapy. pp. 334-342. ISSN 0753-3322

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Abstract

In the current study, a new tetrahydroingenol diterpene isolated from Euphorbia erythradenia, 7,13-diacetyl-5-angeloyl-20-nicotinyl-3-propionyl-1,2,6,7-tetrahydroingenol (DANPT), were tested for the molecular mechanism of its anti-cancer activity in two human melanoma cancer cell lines, A375 and HMCB. DANPT was found cytotoxic against A375 and HMCB cells with IC50 value of 15.37 +/- 2.6 mM and 15.62 +/- 1.89 mu M, respectively. Flow cytometric analysis showed that DANPT halted the A375 and HMCB cells in G2/M phase and induced apoptosis in a dose-dependent manner. Cell cycle arrest was associated with down-regulation of cyclin B and Cdk-1 and subsequent up-regulation of p53 and p21. Moreover, DANPT induced Bax and inhibited Bcl-2 expression, which results in increasing Bax/Bcl-2 ratio and activation of caspase-3. Furthermore, the apoptotic effect of DANPT was also related to ROS production and loss of mitochondrial membrane potential (Delta Ym). Overall, our results suggest that DANPT can inhibit proliferation of human melanoma cancer cells by promoting apoptosis and inducing cell cycle arrest and therefore, it can be a promising natural agent for the treatment of melanoma cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.

Item Type: Article
Keywords: apoptosis melanoma euphorbia erythradenia tetrahydroingenol cancer cytotoxic activity mechanisms chemistry lines
Divisions: Faculty of Pharmacy and Pharmaceutical Sciences > Department of Clinical Biochemistry
Isfahan Pharmaceutical Sciences Research center
Page Range: pp. 334-342
Journal or Publication Title: Biomedicine & Pharmacotherapy
Journal Index: ISI
Volume: 86
Identification Number: https://doi.org/10.1016/j.biopha.2016.12.029
ISSN: 0753-3322
Depositing User: مهندس مهدی شریفی
URI: http://eprints.mui.ac.ir/id/eprint/811

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