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Icariside II induces cell cycle arrest and apoptosis in human glioblastoma cells through suppressing Akt activation and potentiating FOXO3a activity.

ABSTRACT: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and currently chemotherapeutic options for GBM are very limited. Given the poor prognosis, the development of novel anti-GBM agents is quite urgent. Using two human glioma cells (U87 and A172 cells), we demonstrated that Icariside II (ICA II), an active flavonoid compound derived from Epimedium koreanum, could inhibit GBM cell growth in a dose dependent manner. Wound healing data suggested that ICA II also inhibited the migration of human glioma cells. Mechanistically, ICA II induced apoptosis and cell cycle arrest, and this cytotoxic effect was dependent on the reduction of Forkhead box O3a(FOXO3a) phosphorylation mediated by Akt and the enrichment of nuclear FOXO3a, which initiated the transcription of p21/p27. Importantly, the cytotoxic effect induced by ICA II could be reversed by silencing the expression of FOXO3a, suggesting the critical role of FOXO3a in this process. Taken together, we propose ICA II as a potential novel anti-GBM candidate with a mechanism of inhibiting cell proliferation and inducing apoptosis through suppressing Akt activation and potentiating FOXO3a activity.

SUBMITTER: Quan K

PROVIDER: S-EPMC5446533 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Icariside II induces cell cycle arrest and apoptosis in human glioblastoma cells through suppressing Akt activation and potentiating FOXO3a activity.

Quan Kai K Zhang Xin X Fan Kun K Liu Peixi P Yue Qi Q Li Bo B Wu Jinfeng J Liu Baojun B Xu Yang Y Hua Wei W Zhu Wei W

American journal of translational research 20170515 5

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and currently chemotherapeutic options for GBM are very limited. Given the poor prognosis, the development of novel anti-GBM agents is quite urgent. Using two human glioma cells (U87 and A172 cells), we demonstrated that Icariside II (ICA II), an active flavonoid compound derived from <i>Epimedium koreanum</i>, could inhibit GBM cell growth in a dose dependent manner. Wound healing data suggested that ICA II also inh ...[more]

PMID: 28560001

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Project description:BackgroundPlants have proved to be an important source of anti-cancer drugs. Here we have investigated the cytotoxic action of an aqueous extract of Fagonia cretica, used widely as a herbal tea-based treatment for breast cancer.Methodology/principal findingsUsing flow cytometric analysis of cells labeled with cyclin A, annexin V and propidium iodide, we describe a time and dose-dependent arrest of the cell cycle in G0/G1 phase of the cell cycle and apoptosis following extract treatment in MCF-7 (WT-p53) and MDA-MB-231 (mutant-p53) human breast cancer cell lines with a markedly reduced effect on primary human mammary epithelial cells. Analysis of p53 protein expression and of its downstream transcription targets, p21 and BAX, revealed a p53 associated growth arrest within 5 hours of extract treatment and apoptosis within 24 hours. DNA double strand breaks measured as ?-H2AX were detected early in both MCF-7 and MDA-MB-231 cells. However, loss of cell viability was only partly due to a p53-driven response; as MDA-MB-231 and p53-knockdown MCF-7 cells both underwent cell cycle arrest and death following extract treatment. p53-independent growth arrest and cytotoxicity following DNA damage has been previously ascribed to FOXO3a expression. Here, in MCF-7 and MDA-MB-231 cells, FOXO3a expression was increased significantly within 3 hours of extract treatment and FOXO3 siRNA reduced the extract-induced loss of cell viability in both cell lines.Conclusions/significanceOur results demonstrate for the first time that an aqueous extract of Fagonia cretica can induce cell cycle arrest and apoptosis via p53-dependent and independent mechanisms, with activation of the DNA damage response. We also show that FOXO3a is required for activity in the absence of p53. Our findings indicate that Fagonia cretica aqueous extract contains potential anti-cancer agents acting either singly or in combination against breast cancer cell proliferation via DNA damage-induced FOXO3a and p53 expression.

Dataset Information

Icariside II induces cell cycle arrest and apoptosis in human glioblastoma cells through suppressing Akt activation and potentiating FOXO3a activity.

Publications

Icariside II induces cell cycle arrest and apoptosis in human glioblastoma cells through suppressing Akt activation and potentiating FOXO3a activity.

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