Effects of cordycepin on HepG2 and EA.hy926 cells: Potential antiproliferative, antimetastatic and anti‑angiogenic effects on hepatocellular carcinoma

Lu,Haisheng; Li,Xiting; Zhang,Jianying; Shi,Hui; Zhu,Xiaofeng; He,Xiaoshun

doi:10.3892/ol.2014.1965

Effects of cordycepin on HepG2 and EA.hy926 cells: Potential antiproliferative, antimetastatic and anti‑angiogenic effects on hepatocellular carcinoma

Authors:
- Haisheng Lu
- Xiting Li
- Jianying Zhang
- Hui Shi
- Xiaofeng Zhu
- Xiaoshun He
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Affiliations: Organ Transplantation Center, First Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Periodontology, Guanghua School of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China, Department of Radiology, The Affiliated Hexian Memorial Hospital, Southern Medical University, Guangzhou, Guangdong 511400, P.R. China
Published online on: March 11, 2014 https://doi.org/10.3892/ol.2014.1965
Pages: 1556-1562

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Abstract

Hepatocellular carcinoma (HCC) is a hypervascular tumor and accumulating evidence suggests that angiogenesis plays an important role in HCC development. Cordycepin, also known as 3'‑deoxyadenosine, is a derivative of adenosine, and numerous cellular enzymes cannot differentiate the two. The aim of the present study was to determine whether cordycepin regulates proliferation, migration and angiogenesis in a human umbilical vein endothelial cell line (EA.hy926) and in a hepatocellular carcinoma cell line (HepG2). MTT was used to assess cell proliferation. Apoptosis was analyzed by flow cytometry (propidium iodide staining). Transwell and wound healing assays were used to analyze the migration and invasion of HepG2 and EA.hy926 cells. Angiogenesis in EA.hy926 cells was assessed using a tube formation assay. Cordycepin strongly suppressed HepG2 and EA.hy926 cell proliferation in a dose‑ and time‑dependent manner. Cordycepin induced EA.hy926 cell apoptosis in a dose‑dependent manner (2,000 µg/ml: 50.20±1.55% vs. 0 µg/ml: 2.62±0.19%; P<0.01). Cordycepin inhibited EA.hy926 cell migration (percentage of wound healing area, 2,000 µg/ml: 3.45±0.29% vs. 0 µg/ml: 85.48±0.84%; P<0.05), as well as tube formation (total length of tubular structure, 1,000 µg/ml: 107±39 µm vs. 0 µg/ml: 936±56 µm; P<0.05). Cordycepin also efficiently inhibited HepG2 cell invasion and migration. High‑performance liquid chromatography analysis of the cytosol from EA.hy926 cells showed that cordycepin was stable for 3 h. In conclusion, cordycepin not only inhibited human HepG2 cell proliferation and invasion, but also induced apoptosis and inhibited migration and angiogenesis in vascular endothelial cells, suggesting that cordycepin may be used as a novel anti‑angiogenic therapy in HCC.

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