TY - JOUR
T1 - Growth inhibition effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid on colorectal carcinoma cells and colon carcinoma-bearing mice
AU - Ye, Hua
AU - Wu, Qiong
AU - Guo, Meng
AU - Wu, Kefeng
AU - Lv, Yingnian
AU - Yu, Fengyan
AU - Liu, Yi
AU - Gao, Xiaosheng
AU - Zhu, Yuzhen
AU - Cui, Liao
AU - Liang, Nianci
AU - Yun, Tu
AU - Li, Li
AU - Zheng, Xuebao
N1 - Funding Information:
The present study was supported by the National Natural Science Foundation of China (grant nos. 81173240 and 3987099)
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - Cell apoptosis
KW - Colorectal cancer
KW - Mitochondrial pathway
KW - Xenograft
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U2 - 10.3892/mmr.2016.4950
DO - 10.3892/mmr.2016.4950
M3 - Article
C2 - 26935771
AN - SCOPUS:84963830873
VL - 13
SP - 3525
EP - 3532
JO - Molecular Medicine Reports
JF - Molecular Medicine Reports
SN - 1791-2997
IS - 4
ER -