Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
Breast Cancer Res Treat. 2012 Sep;135(2):445-58. doi: 10.1007/s10549-012-2175-5. Epub 2012 Jul 28.
Tumor metastasis is the main cause of cancer-related deaths of patients. Breast cancer is highly malignant with considerable metastatic potential, which urges the necessity for developing novel potential drug candidate to prevent tumor metastasis. Here, we report our finding with Cucurbitacin E (CuE, α-elaterin), a tetracyclic triterpenes compound isolated from Cucurbitaceae. The potency of CuE on breast cancer metastasis inhibition was assessed in vivo and in vitro. In our animal experiments, intraperitoneal administrations of CuE significantly inhibited breast tumor metastasis to the lung without affecting apoptosis or proliferation of inoculated 4T1 and MDA-MB-231 breast cancer cells. Treatment of metastatic breast tumor cells with CuE markedly blocked tumor cell migration and invasion in vitro. Subsequent studies showed that CuE impaired Arp2/3-dependent actin polymerization and suppressed Src/FAK/Rac1/MMP involved pathway. Overall, our data demonstrate that CuE blocks breast cancer metastasis by suppressing tumor cell migration and invasion. We provide first evidence of a novel role for CuE as a potential candidate for treating breast cancer metastasis.
肿瘤转移是导致患者癌症相关死亡的主要原因。乳腺癌恶性程度高，转移潜能大，因此迫切需要开发新的潜在药物候选物来预防肿瘤转移。在这里，我们报告了葫芦素 E（CuE，α-别瓜氨酸）的研究结果，CuE 是一种从葫芦科植物中分离得到的四环三萜类化合物。我们在体内和体外评估了 CuE 对乳腺癌转移抑制的作用。在动物实验中，CuE 的腹腔给药显著抑制了乳腺癌向肺部的转移，而不影响接种的 4T1 和 MDA-MB-231 乳腺癌细胞的凋亡或增殖。CuE 处理转移性乳腺癌细胞可显著阻断体外肿瘤细胞的迁移和侵袭。随后的研究表明，CuE 可破坏 Arp2/3 依赖性肌动蛋白聚合，并抑制 Src/FAK/Rac1/MMP 相关通路。总体而言，我们的数据表明，CuE 通过抑制肿瘤细胞的迁移和侵袭来阻止乳腺癌转移。我们首次证明了 CuE 作为治疗乳腺癌转移的潜在候选药物的新作用。
