Antiproliferative effect of ME3738, a derivative of soyasapogenol, on hepatocellular carcinoma cell lines in vitro and in vivo

Ogasawara,Sachiko; Akiba,Jun; Nakayama,Masamichi; Kusano,Hironori; Yano,Hirohisa

doi:10.3892/br.2016.792

Antiproliferative effect of ME3738, a derivative of soyasapogenol, on hepatocellular carcinoma cell lines in vitro and in vivo

Authors:
- Sachiko Ogasawara
- Jun Akiba
- Masamichi Nakayama
- Hironori Kusano
- Hirohisa Yano
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Affiliations: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Diagnostic Pathology, Kurume University Hospital and Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: October 25, 2016 https://doi.org/10.3892/br.2016.792
Pages: 731-736

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Abstract

Soyasapogenol, an aglycon of soyasaponin, ameliorates liver injury induced by concanavalin A in mice. A derivative of soyasapogenol, 22β‑methoxyolean‑12‑ene‑3β, 24(4β)‑diol (ME3738), was reported to induce the gene expression of interferon (IFN)‑β in hepatitis C virus replicon cells. The effect of ME3738 on hepatocellular carcinoma (HCC) cell lines was investigated in the present study. A total of 11 HCC cell lines were cultured in medium containing 0‑10 µM ME3738, and after 24, 48, or 72 h of culture, morphological observation and MTT cell growth assays were performed. Furthermore, the effects of ME3738 with or without PEG‑IFN‑α‑2b on cell lines were investigated. Induction of apoptosis was examined on cells treated with 1 µM of ME3738 using an Annexin V assay. The effect of ME3738 (0.63 and 2.5 µM) on cell cycle progression was analyzed on two cell lines. The mice with subcutaneous tumors were divided into four groups: i) Control; ii) ME3738 alone; iii) PEG‑IFN‑α‑2b alone and iv) ME3738+PEG‑IFN‑α‑2b (combination). ME3738 was mixed with food (1.5 mg/g) and was taken orally for 15 days. PEG‑IFN‑α‑2b (1,920 IU/mouse) was subcutaneously injected twice a week for two consecutive weeks. On day 15, the mice were sacrificed and the tumors were resected. A dose‑dependent anti‑proliferative effect was observed to various degrees in all the HCC cell lines in vitro. This inhibitory effect reached its maximal level 24 h after the treatment and the 50% inhibitory dose was between 0.8 and 2.4 µM. The combination treatment did not show a synergistic effect. Induction of apoptosis was not observed. Cell cycle arrest at S‑phase was observed in two of the examined cell lines. On day 15, the tumor volume of mice receiving ME3738, PEG‑IFN‑α‑2b, and ME3738+PEG‑IFN‑α‑2b was 69, 30, and 33%, respectively, of the control tumor volume. ME3738 induced antiproliferative effects on the HCC cells in vitro and in vivo. The data suggested potential clinical application of ME3738.

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