Department of Pharmacology, Capital Medical University, Beijing, China.
Oncol Res. 2014;21(5):247-59. doi: 10.3727/096504014X13946388748910.
Cloves (Syzygium aromaticum) have been used as a traditional Chinese medicinal herb for thousands of years. Cloves possess antiseptic, antibacterial, antifungal, and antiviral properties, but their potential anticancer activity remains unknown. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of ethyl acetate extract of cloves (EAEC) and the potential bioactive components responsible for its antitumor activity. The effects of EAEC on cell growth, cell cycle distribution, and apoptosis were investigated using human cancer cell lines. The molecular changes associated with the effects of EAEC were analyzed by Western blot and (qRT)-PCR analysis. The in vivo effect of EAEC and its bioactive component was investigated using the HT-29 tumor xenograft model. We identified oleanolic acid (OA) as one of the components of EAEC responsible for its antitumor activity. Both EAEC and OA display cytotoxicity against several human cancer cell lines. Interestingly, EAEC was superior to OA and the chemotherapeutic agent 5-fluorouracil at suppressing growth of colon tumor xenografts. EAEC promoted G0/G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. Treatment with EAEC and OA selectively increased protein expression of p21(WAF1/Cip1) and γ-H2AX and downregulated expression of cell cycle-regulated proteins. Moreover, many of these changes were at the mRNA level, suggesting transcriptional regulation by EAEC treatment. Our results demonstrate that clove extract may represent a novel therapeutic herb for the treatment of colorectal cancer, and OA appears to be one of the bioactive components.
丁香（Syzygium aromaticum）作为一种传统的中草药，已经使用了数千年。丁香具有防腐、抗菌、抗真菌和抗病毒的特性，但它们潜在的抗癌活性尚不清楚。在这项研究中，我们研究了丁香乙酸乙酯提取物（EAEC）的体外和体内抗肿瘤作用及其潜在的生物活性成分的抗肿瘤活性。用人类癌细胞系研究 EAEC 对细胞生长、细胞周期分布和细胞凋亡的影响。通过 Western blot 和（qRT）-PCR 分析分析与 EAEC 作用相关的分子变化。使用 HT-29 肿瘤异种移植模型研究 EAEC 及其生物活性成分的体内作用。我们确定齐墩果酸（OA）是 EAEC 抗肿瘤活性的成分之一。EAEC 和 OA 均对几种人类癌细胞系表现出细胞毒性。有趣的是，EAEC 在抑制结肠肿瘤异种移植生长方面优于 OA 和化疗药物 5-氟尿嘧啶。EAEC 以剂量依赖性方式促进 G0/G1 细胞周期停滞并诱导细胞凋亡。用 EAEC 和 OA 处理可选择性地上调 p21（WAF1/Cip1）和γ-H2AX 的蛋白表达，并下调细胞周期调节蛋白的表达。此外，这些变化中的许多是在 mRNA 水平上，表明 EAEC 处理的转录调控。我们的结果表明，丁香提取物可能代表一种治疗结直肠癌的新型治疗草药，而 OA 似乎是生物活性成分之一。
