Growth inhibition effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid on colorectal carcinoma cells and colon carcinoma-bearing mice

Ye,Hua; Wu,Qiong; Guo,Meng; Wu,Kefeng; Lv,Yingnian; Yu,Fengyan; Liu,Yi; Gao,Xiaosheng; Zhu,Yuzhen; Cui,Liao; Liang,Nianci; Yun,Tu; Li,Li; Zheng,Xuebao

doi:10.3892/mmr.2016.4950

Growth inhibition effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid on colorectal carcinoma cells and colon carcinoma-bearing mice

Authors:
- Hua Ye
- Qiong Wu
- Meng Guo
- Kefeng Wu
- Yingnian Lv
- Fengyan Yu
- Yi Liu
- Xiaosheng Gao
- Yuzhen Zhu
- Liao Cui
- Nianci Liang
- Tu Yun
- Li Li
- Xuebao Zheng
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Affiliations: Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524023, P.R. China
Published online on: February 29, 2016 https://doi.org/10.3892/mmr.2016.4950
Pages: 3525-3532

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Abstract

The aim of the present study was to investigate the mechanism underlying the antitumor effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) in colorectal cancer (CRC). 5F was isolated and used to treat C26 murine colon carcinoma cells, a xenograft tumor mouse model (induced by C26 cells) and a CRC mouse model [induced by 1,2-dimethylhydrazine (DMH)/dextran sodium sulfate (DSS)]. C26 cell growth was inhibited by 5F in a dose- and time-dependent manner in vitro. In addition, 5F induced cell apoptosis and cell cycle arrest in the G2 phase, increased the activity of caspase-3 and caspase-9, but did not affect the activity of cascase‑8, suggesting that 5F induced apoptosis via activation of the mitochondrial signaling pathway rather than the death‑receptor signaling pathway. Furthermore, treatment of C26 cells with 5F resulted in upregulation of cyclin‑dependent kinase inhibitor 1A (p21, Cip1), Bcl‑2‑associated X protein, nuclear factor of κ light polypeptide gene enhancer in B‑cells inhibitor, α and downregulation of B‑cell lymphoma 2, nuclear factor κ‑light‑chain enhancer of activated B cells and survivin. In vivo animal models demonstrated that 5F treatment protected mice from carcinogenesis induced by DMH/DSS and markedly decreased the xenograft tumor weight with minimal side effects. Therefore, 5F may have potential as an anti-CRC therapeutic agent for use in the clinical setting.

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