Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Biomolecules. 2019 Jul 13;9(7):278. doi: 10.3390/biom9070278.
Triple-negative breast cancers (TNBCs) are hard-to-treat breast tumors with poor prognosis, which need to be treated by chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in proliferation, metastasis, and invasion of cancer cells. Therefore, research on searching for promising compounds with metabolism that suppress phosphorylation or transcription of STAT3 in TNBC cells is important. Farfarae Flos is well known as a traditional medicine for treating inflammation. However, few studies have shown that sesquiterpenoids from Farfarae Flos have an anticancer effect. In this study, efficient separation methods and an MTT assay were conducted to isolate an anticancer compound from Farfarae Flos against TNBC MDA-MB-231 cells. Here, 7β-(3-Ethyl--crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro--notonipetranone (ECN), a compound isolated from Farfarae Flos showed a potent cytotoxic effect on MDA-MB-231 cells. ECN inhibited JAK-STAT3 signaling and suppressed the expression of STAT3 target genes. In addition, ECN induced apoptosis through both extrinsic and intrinsic pathways. Furthermore, we investigated that ECN inhibited the growth of tumors by intraperitoneal administration in mice injected with MDA-MB-231 cells. Therefore, ECN can be an effective chemotherapeutic agent for breast cancer treatment.
三阴性乳腺癌（TNBC）是一种预后不良的难治性乳腺癌，需要进行化疗。信号转导子和转录激活子 3（STAT3）是一种转录因子，参与癌细胞的增殖、转移和侵袭。因此，研究寻找具有代谢抑制 TNBC 细胞中 STAT3 磷酸化或转录的有前途的化合物非常重要。款冬花是一种传统的治疗炎症的药物。然而，很少有研究表明款冬花中的倍半萜类化合物具有抗癌作用。在这项研究中，采用高效分离方法和 MTT 测定法，从款冬花中分离出一种针对 TNBC MDA-MB-231 细胞的抗癌化合物。在这里，从款冬花中分离得到的化合物 7β-（3-乙基-巴豆酰氧基）-1α-（2-甲基丁酰氧基）-3,14-去氢-诺桐皮酮（ECN）对 MDA-MB-231 细胞表现出强烈的细胞毒性作用。ECN 抑制 JAK-STAT3 信号通路，并抑制 STAT3 靶基因的表达。此外，ECN 通过外在和内在途径诱导细胞凋亡。此外，我们研究了 ECN 通过腹腔注射 MDA-MB-231 细胞的小鼠模型抑制肿瘤生长的作用。因此，ECN 可以成为治疗乳腺癌的有效化疗药物。
