Hinokitiol Inhibits Cell Growth through Induction of S-Phase Arrest and Apoptosis in Human Colon Cancer Cells and Suppresses Tumor Growth in a Mouse Xenograft Experiment
Hinokitiol Inhibits Cell Growth through Induction of S-Phase Arrest and Apoptosis in Human Colon Cancer Cells and Suppresses Tumor Growth in a Mouse Xenograft Experiment
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DOI：
10.1021/np4005135
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发表时间：
2013-12-01
影响因子：
5.1
通讯作者：
Yoo, Hwan-Soo
中科院分区：
文献类型：
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作者：
Lee, Youn-Sun;Choi, Kyeong-Mi;Yoo, Hwan-Soo
Hinokitiol(1)是一种与托洛酮相关的天然化合物，可诱导细胞凋亡，并具有抗炎、抗氧化和抗肿瘤活性。本研究观察了I对人结肠癌细胞生长和小鼠移植瘤的抑制作用。人结肠癌细胞株HCT-116和SW-620对I的敏感性相似，IC50值分别为4.5和4.4微米。化合物I诱导S期细胞周期停滞，降低细胞周期蛋白A、细胞周期蛋白E和细胞周期蛋白CDK2的表达水平。反之，1可增加CDK抑制剂p21的表达。化合物1降低Bcl2的表达，增加Bax的表达，并切割caspase-9和caspase-3。用雄性BALB/c裸鼠分别皮下接种HCT-116和SW-620细胞，观察灌胃给药对肿瘤形成的影响。在两种情况下，1(100 mg/kg)治疗组小鼠的肿瘤体积和肿瘤重量都有所减少。这些结果提示化合物1对人结肠癌的抑制作用可能是通过细胞周期停滞和细胞凋亡来实现的。
Hinokitiol (1), a tropolone-related natural compound, induces apoptosis and has anti-inflammatory, antioxidant, and antitumor activities. In this study, the inhibitory effects of I were investigated on human colon cancer cell growth and tumor formation of xenograft mice. HCT-116 and SW-620 cells derived from human colon cancers were found to be similarly susceptible to I, with IC50 values of 4.5 and 4.4 mu M, respectively. Compound I induced S-phase arrest in the cell cycle progression and decreased the expression levels of cyclin A, cyclin E, and Cdk2. Conversely, 1 increased the expression of p21, a Cdk inhibitor. Compound 1 decreased Bcl-2 expression and increased the expression of Bax, and cleaved caspase-9 and -3. The effect of I on tumor formation when administered orally was evaluated in male BALB/c-nude mice implanted intradermally separately with HCT-116 and SW-620 cells. Tumor volumes and tumor weights in the mice treated with 1 (100 mg/kg) were decreased in both cases. These results suggest that the suppression of tumor formation by compound 1 in human colon cancer may occur through cell cycle arrest and apoptosis.