Department of Pharmacology & Therapeutics, Faculty of Medicine & Health Sciences, UAE University, Al-Ain, PO Box: 17666, United Arab Emirates.
Eur J Pharmacol. 2011 Oct 1;668(1-2):25-34. doi: 10.1016/j.ejphar.2011.06.023. Epub 2011 Jun 27.
Breast cancer is a major challenge for pharmacologists to develop new drugs to improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in vivo. We investigated the impact of Frondoside A on human breast cancer cell survival, migration and invasion in vitro, and on tumor growth in nude mice, using the human estrogen receptor-negative breast cancer cell line MDA-MB-231. The non-tumorigenic MCF10-A cell line derived from normal human mammary epithelium was used as control. Frondoside A (0.01-5 μM) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5 μM at 24h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5 μM at 24 h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1 (apoptotic) cell fraction through the activation of p53, and subsequently the caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In vivo, Frondoside A (100 μg/kg/dayi.p. for 24 days) strongly decreased the growth of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side-effects. Moreover, we found that Frondoside A could enhance the killing of breast cancer cells induced by the chemotherapeutic agent paclitaxel. These findings identify Frondoside A as a promising novel therapeutic agent for breast cancer.
乳腺癌是药理学家开发新药以提高癌症患者生存率的主要挑战。 Frondoside A 是从海参 Cucumaria frondosa 中分离出的一种三萜糖苷。已经证明 Frondoside A 可以抑制体外和体内胰腺癌细胞的生长。我们研究了 Frondoside A 对人乳腺癌细胞 MDA-MB-231 体外存活、迁移和侵袭以及裸鼠肿瘤生长的影响。非致瘤性 MCF10-A 细胞系源自正常人乳腺上皮，用作对照。 Frondoside A（0.01-5 μM）以浓度和时间依赖性方式降低乳腺癌细胞的活力，在 24 小时时 50％有效浓度（EC50）为 2.5 μM。 MCF10-A 细胞对 Frondoside A 的细胞毒性作用的抵抗力更强（在 24 小时时 EC50 超过 5 μM）。在 MDA-MB-231 细胞中，Frondoside A 通过激活 p53，随后激活 caspase 9 和 3/7 细胞死亡途径，有效地增加了亚 G1（凋亡）细胞分数。此外，Frondoside A 诱导 MDA-MB-231 细胞迁移和侵袭的浓度依赖性抑制。在体内，Frondoside A（100 μg/kg/天腹腔注射 24 天）强烈抑制了无胸腺小鼠 MDA-MB-231 肿瘤异种移植物的生长，没有明显的毒副作用。此外，我们发现 Frondoside A 可以增强化疗药物紫杉醇诱导的乳腺癌细胞杀伤作用。这些发现表明 Frondoside A 是一种有前途的新型乳腺癌治疗药物。
