Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells

Sun,Li; Peng,Qisong; Qu,Lili; Gong,Lailing; Si,Jin

doi:10.3892/mmr.2014.3007

Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells

Authors:
- Li Sun
- Qisong Peng
- Lili Qu
- Lailing Gong
- Jin Si
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Affiliations: Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China, Department of Laboratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China
Published online on: November 26, 2014 https://doi.org/10.3892/mmr.2014.3007
Pages: 3094-3100

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Abstract

Icaritin is an active ingredient derived from the plant Herba epimedium, which exhibits various pharmacological and biological activities. However, the function, and the underlying mechanisms of icaritin on the growth of SMMC‑7721 human hepatoma cells have yet to be elucidated. The present study aimed to investigate the function and underlying mechanisms of icaritin in the growth of SMMC‑7721 cells. The cells were treated with varying concentrations of icaritin for 12, 24 and 48 h, respectively, prior to cytotoxic analysis. Apoptosis of SMMC‑7721 cells following treatment with icaritin was measured using flow cytometry. The gene expression of mitochondria‑ and Fas‑mediated caspase‑dependent pathways was detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. Statistical analysis was performed by Student's t‑test and one‑way analysis or variance. The present study demonstrated that treatment with icaritin significantly inhibited growth, and induced apoptosis of SMMC‑7721 cells, in a time‑ and dose‑dependent manner. In addition, icaritin triggered the mitochondrial/caspase apoptotic pathway, by decreasing the Bcl‑2/Bax protein ratio and increasing activation of caspase‑3. Icaritin also activated the Fas‑mediated apoptosis pathway, as was evident by the increased expression levels of Fas and activation of caspase‑8. These data suggest that icaritin may be a potent growth inhibitor and induce apoptosis of SMMC‑7721 cells through the mitochondria‑ and Fas‑mediated caspase‑dependent pathways. The present study may provide experimental evidence for preclinical and clinical evaluations of icaritin for HCC therapy.

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