Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.
复制标题
DOI：
10.1371/journal.pone.0053087
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
De Wever O
中科院分区：
文献类型：
--
作者：
Attoub S;Arafat K;Gélaude A;Al Sultan MA;Bracke M;Collin P;Takahashi T;Adrian TE;De Wever O
肿瘤学家和药理学家面临的一个主要挑战是开发毒性较小的药物，以提高肺癌患者的生存率。Frondoside A是从海参Cucumaria frondosa中分离得到的一种三萜苷类化合物，具有很高的安全性。我们研究了Frondoside A在体外对存活、迁移和侵袭的影响，以及单独和与顺铂联合在体内对肿瘤生长、转移和血管生成的影响。Frondoside A通过半胱天冬酶3/7依赖性细胞死亡途径在24小时内引起LNM 35、A549、NCI-H460-Luc 2、MDA-MB-435、MCF-7和HepG 2的活力的浓度依赖性降低。24 h时的IC 50浓度（产生半数最大抑制）为1.7 - 2.5 µM的Frondoside A。此外，Frondoside A在体外诱导细胞迁移、侵袭和血管生成的时间和浓度依赖性抑制。Frondoside A（0.01和1 mg/kg/d，连续25天腹腔注射）能显著抑制LNM 35裸鼠移植瘤的生长、血管生成和淋巴结转移，无明显毒副作用。在CAM血管生成试验中，Frondoside A（0.1-0.5 µM）也显著阻止了基础和bFGF诱导的血管生成。此外，Frondoside A增强了由化疗剂顺铂诱导的肺肿瘤生长的抑制。这些发现确定Frondoside A作为一种有前途的新型肺癌治疗药物。
A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1–0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer.
登录
查看更多内容
影响因子：
5
作者：
Al Marzouqi, Nadia;Iratni, Rabah;Attoub, Samir
通讯作者：
Attoub, Samir
DOI：
10.1196/annals.1414.025
发表时间：
2008-01-01
期刊：
RECENT ADVANCES IN CLINICAL ONCOLOGY
影响因子：
--
作者：
Li, X.;Roginsky, A. B.;Adrian, T. E.
通讯作者：
Adrian, T. E.
影响因子：
2.9
作者：
Roginsky, Alexandra B.;Ding, Xian-Zhong;Adrian, Thomas E.
通讯作者：
Adrian, Thomas E.
影响因子：
5.6
作者：
HARRISHOOKER, SA;GAJDUSEK, CM;SCHWARTZ, SM
通讯作者：
SCHWARTZ, SM
DOI：
10.4236/jbpc.2012.32018
发表时间：
2012-01-01
期刊：
Journal of Biophysical Chemistry
影响因子：
--
作者：
Kuno, T.;Tsukamoto, T.;Tanaka, T.
通讯作者：
Tanaka, T.