Ahn Ji-Hye, Lee Tae-Won, Kim Ki-Hee, Byun Hoyong, Ryu Byeol, Lee Kyung-Tae, Jang Dae Sik, Choi Jung-Hye
Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul, South Korea.
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, South Korea.
Phytother Res. 2015 Sep;29(9):1330-1338. doi: 10.1002/ptr.5385. Epub 2015 Jun 10.
Cyperus rotundus (Cyperaceae) has been widely used in traditional medicine for the treatment of various diseases, including cancer. Although an anti-tumour effect has been suggested for C. rotundus, the anti-tumour effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The n-hexane fraction of an ethanol extract of C. rotundus rhizomes was found to inhibit cell growth in ovarian cancer (A2780, SKOV3 and OVCAR3) and endometrial cancer (Hec1A and Ishikawa) cells. Among the thirteen sesquiterpenes isolated from the n-hexane fraction, some patchoulane-type compounds, but not eudesmane-type compounds, showed moderate cytotoxic activity in human ovarian cancer cells. In particular, the patchoulane sesquiterpene 6-acetoxy cyperene had the most potent cytotoxicity. In this regard, propidium iodide/Annexin V staining and terminal deoxynucleotidyl transferase dUTP (deoxynucleotide triphosphate) nick end labeling assay were performed to study cell cycle progression and apoptosis. 6-acetoxy cyperene induced apoptosis, as shown by the accumulation of sub-G1 and apoptotic cells. Furthermore, treatment with 6-acetoxy cyperene stimulated the activation of caspase-3, caspase-8 and caspase-9 and poly(ADP-ribose)polymerase in a dose-dependent manner. Pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of 6-acetoxy cyperene. Taken together, these data suggest that 6-acetoxy cyperene, a patchoulane-type sesquiterpene isolated from C. rotundus rhizomes, is an anti-tumour compound that causes caspase-dependent apoptosis in ovarian cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.
香附子（莎草科）在传统医学中已被广泛用于治疗包括癌症在内的各种疾病。尽管已有研究表明香附子具有抗肿瘤作用，但其生物活性化合物的抗肿瘤效果及潜在分子机制仍知之甚少。研究发现，香附子根茎乙醇提取物的正己烷部位可抑制卵巢癌（A2780、SKOV3和OVCAR3）及子宫内膜癌（Hec1A和Ishikawa）细胞的生长。从正己烷部位分离出的13种倍半萜中，一些广藿香烷型化合物而非桉叶烷型化合物在人卵巢癌细胞中表现出中等程度的细胞毒性活性。特别是广藿香烷倍半萜6-乙酰氧基莎草烯具有最强的细胞毒性。为此，进行了碘化丙啶/膜联蛋白V染色及末端脱氧核苷酸转移酶dUTP缺口末端标记试验以研究细胞周期进程和细胞凋亡。6-乙酰氧基莎草烯诱导了细胞凋亡，表现为亚G1期细胞和凋亡细胞的积累。此外，用6-乙酰氧基莎草烯处理可剂量依赖性地刺激半胱天冬酶-3、半胱天冬酶-8和半胱天冬酶-9以及聚（ADP-核糖）聚合酶的激活。用半胱天冬酶抑制剂预处理可中和6-乙酰氧基莎草烯的促凋亡活性。综上所述，这些数据表明，从香附子根茎中分离出的广藿香烷型倍半萜6-乙酰氧基莎草烯是一种抗肿瘤化合物，可在卵巢癌细胞中引起半胱天冬酶依赖性凋亡。版权所有© 2015约翰威立父子有限公司。
