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Hedyotis diffusa Willd extract inhibits the growth of human glioblastoma cells by inducing mitochondrial apoptosis via AKT/ERK pathways

Authors Zhang, Yan; Xie, Rui-Fan; Xiao, Qun-Gen; Li, Ran; Shen, Xiao-Li; Zhu, Xin-Gen

Journal JOURNAL OF ETHNOPHARMACOLOGY , DEC 2 2014,:158

DOI 10.1016/j.jep.2014.10.017 PubMed 25456437

Abstract Ethnopharmacological relevance: Hedyotis diffusa Willd (Rubiaceae) (HDW) has been widely applied for the treatment of tumors, inflammation and toxication in traditional Chinese medicine. The antitumor effect of HDW on glioblastoma has been rarely reported. We aim to evaluate the activity of this extract and explore the underlying mechanism in U87 human glioblastoma cell line.Materials and methods: Cytotoxicity of HDW extract on U87 cells was measured by MTT assay. Apoptosis, cell cycle arrest and mitochondrial membrane potential (MMP) collapse induced by HDW extract were determined by flow cytometry. Caspase activity was analyzed based on colorimetric assay with a microplate spectrophotometer. Protein expression was examined by Western blot.Results: HDW extract suppressed U87 cells growth in a dose- and time-dependent manner. Flow cytometry showed that HDW extract induced significant apoptosis, S/G2-M phase arrest and MMP collapse in U87 cells. Furthermore, dose-dependent activation of caspase-3, Bcl-2, Bax and ERIC was observed with HDW extract treatment. Decreased Bcl-2/Bax ratio and Ala suppression were readily found as well.Conclusions: Induction of mitochondria-mediated apoptosis played an essential role in antitumor activity of HDW extract in 1387 cells, in which ERKs and Ala signaling proteins were also involved. These findings contributed to the feasibility of using HDW extract in glioblastoma treatment and the understanding of the molecular mechanism (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Species covered 白花蛇舌草 Hedyotis diffusa