Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts
Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts
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DOI：
10.1016/j.ejphar.2011.06.023
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发表时间：
2011-10-01
影响因子：
5
通讯作者：
Attoub, Samir
中科院分区：
文献类型：
--
作者：
Al Marzouqi, Nadia;Iratni, Rabah;Attoub, Samir
乳腺癌是药理学家开发新药以提高癌症患者生存率的重大挑战。 Frondoside A 是一种从海参 (Cucumaria frondosa) 中分离出来的三萜糖苷。已证明 Frondoside A 在体外和体内均可抑制胰腺癌细胞的生长。我们使用人雌激素受体阴性乳腺癌细胞系 MDA-MB-231，研究了 Frondoside A 对人乳腺癌细胞体外存活、迁移和侵袭以及对裸鼠肿瘤生长的影响。源自正常人乳腺上皮的非致瘤性MCF10-A细胞系用作对照。 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，24 小时时 50% 有效浓度 (EC50) 为 2.5 μM。 MCF10-A细胞对Frondoside A的细胞毒性作用具有更强的抵抗力（24小时EC50优于5μM）。在 MDA-MB-231 细胞中，Frondoside A 通过激活 p53 以及随后的 caspase 9 和 3/7 细胞死亡途径，有效增加亚 G1（凋亡）细胞分数。此外，Frondoside A 还可诱导 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，持续 24 天）强烈降低无胸腺小鼠中 MDA-MB-231 肿瘤异种移植物的生长，且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的杀伤作用。这些发现表明 Frondoside A 是一种有前途的新型乳腺癌治疗剂。 (C) 2011 Elsevier B.V. 保留所有权利。
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 mu M) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5 mu M at 24 h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5 mu M 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 mu g/kg/day i.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. (C) 2011 Elsevier B. V. All rights reserved.