Icariside II induces apoptosis via inhibition of the EGFR pathways in A431 human epidermoid carcinoma cells

Wu,Jinfeng; Zuo,Fuguo; Du,Juan; Wong,Pok  Fai; Qin,Haihong; Xu,Jinhua

doi:10.3892/mmr.2013.1557

Icariside II induces apoptosis via inhibition of the EGFR pathways in A431 human epidermoid carcinoma cells

Authors:
- Jinfeng Wu
- Fuguo Zuo
- Juan Du
- Pok Fai Wong
- Haihong Qin
- Jinhua Xu
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Affiliations: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Dermatology, East Hospital, School of Medicine, Tongji University, Shanghai 200120, P.R. China, Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Edward Ford Building A27, Sydney Medical School, The University of Sydney, Darlington, New South Wales 2006, Australia
Published online on: June 26, 2013 https://doi.org/10.3892/mmr.2013.1557
Pages: 597-602

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Abstract

Improvements in skin cancer treatment are likely to derive from novel agents targeting the molecular pathways that promote tumor cell growth and survival. Icariside II (IS) is a metabolite of icariin, which is derived from Herba Epimedii. The aim of the present study was to evaluate the antitumor effects of IS and to determine the mechanism of apoptosis in A431 human epidermoid carcinoma cells. A431 cells were treated with IS (0‑100 µM) for 24 or 48 h and cell viability was detected using the WST‑8 assay. Apoptosis was measured by the Annexin‑V/propidium iodide (PI) flow cytometric assay. Western blot analysis was used to measure the expression of cleaved caspase‑9, cleaved poly ADP ribose polymerase (PARP), phosphorylated signal transducer and activator of transcription 3 (P‑STAT3), phosphorylated extracellular signal-regulated kinase (P‑ERK), and P‑AKT. A431 cells were also pretreated with IS (0‑100 µM) 2 h prior to treatment with epidermal growth factor (EGF; 100 ng/ml) for 10 min. Phosphorylated EGF receptor (P‑EGFR), P‑STAT3, P‑ERK and P‑AKT were detected by western blot analysis. The results demonstrated that IS inhibited the cell viability of the A431 cells in a dose‑dependent manner. Pretreatment with LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor], EGF (an EGFR agonist) and AG1478 (an EGFR inhibitor) partially reversed IS‑induced decreases in cell viability. Treatment with 50 µm IS resulted in an increased number of apoptotic cells mirrored by increases in cleaved caspase‑9 and cleaved PARP. In addition, treatment with 50 µM IS significantly inhibited the activation of the Janus kinase (JAK)‑STAT3 and mitogen‑activated protein kinase (MAPK)‑ERK pathways, but promoted the activation of the PI3K‑AKT pathway. Furthermore, IS effectively inhibited the EGF-induced activation of the EGFR pathways. In conclusion, IS inhibited the cell viability of the A431 cells through the regulation of apoptosis. These effects were mediated, at least in part, by inhibiting the activation of the EGFR pathways.

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