Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis
Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis
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DOI：
10.1021/acs.jafc.6b05376
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发表时间：
2017-03-01
影响因子：
6.1
通讯作者：
Xiao, Hang
中科院分区：
文献类型：
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作者：
Chen, Xuexiang;Wu, Xian;Xiao, Hang
山莓的嫩叶。F.自古以来，在中国就被当作茶饮用。从山茱萸中分离鉴定了一个新的贝壳杉烷型二萜化合物。F.叶为对映贝壳杉-2-酮16 β，17-二羟基-丙酮-缩酮（DEK）。DEK抑制HCT 116人结肠癌细胞的生长，IC 50值为40 +/- 0.21 μ M，而在高达100 μ M时，它对CCD-18 Co人结肠肌成纤维细胞没有引起显著的生长抑制。此外，DEK诱导结肠癌细胞广泛的凋亡和S期细胞周期阻滞。因此，DEK对与细胞增殖、细胞死亡和炎症相关的多种信号蛋白产生了深远的影响。DEK显著上调促凋亡蛋白如裂解的caspase-3、裂解的caspase-9、裂解的PARP、p53、Bax和肿瘤抑制因子p21（ciPl/Waf 1）的表达水平，下调细胞周期调节蛋白如cyclinD 1、CDK 2和CDK 4以及致癌蛋白如EGFR和考克斯-2的水平，并抑制Akt的活化。总的来说，我们的研究结果提供了一个基础，使用DEK作为一个潜在的化学预防剂对结肠癌的发生。
The tender leaves of Rubus corchorifolius L. f. have been consumed as tea for drinking in China since ancient times. In this study, a novel ent-kaurane diterpenoid was isolated and identified from R corchorifolius L. f. leaves as ent-kaur-2-one16 beta,17-dihydroxy-acetone-ketal (DEK). DEK suppressed the growth of HCT116 human colon cancer cells with an IC50 value of 40 +/- 0.21 yM, while it did not cause significant growth inhibition on CCD-18Co human colonic myofibroblasts at up to100 mu M. Moreover, DEK induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells. Accordingly, DEK caused profound effects on multiple signaling proteins associated with cell proliferation, cell death, and inflammation. DEK significantly upregulated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, cleaved caspase-9, cleaved PARP, p53, Bax, and tumor suppressor p21(ciPl/Waf1), downregulated the levels of cell cycle regulating proteins such as cyclinD1, CDK2, and CDK4 and carcinogenic proteins such as EGFR and COX-2, and suppressed the activation of Akt. Overall, our results provide a basis for using DEK as a potential chemopreventive agent against colon carcinogenesis.