Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.
Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.
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DOI：
10.1371/journal.pone.0097622
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sayed KA
中科院分区：
文献类型：
--
作者：
Akl MR;Ayoub NM;Mohyeldin MM;Busnena BA;Foudah AI;Liu YY;Sayed KA
肝细胞生长因子 (HGF)/c-Met 信号轴的失调会上调多种肿瘤细胞功能，包括细胞增殖、存活、分散和运动、上皮间质转化 (EMT)、血管生成、侵袭和转移。 (-)-Oleocanthal 是一种从特级初榨橄榄油中提取的天然环烯醚萜化合物，对不同的癌细胞系具有抗增殖和抗迁移活性。本研究的目的是表征介导 (-)-oleocanthal 治疗的抗癌作用的细胞内机制以及 c-Met 受体信号传导成分在乳腺癌中的潜在参与。结果表明，(-)-oleocanthal 抑制人乳腺癌细胞系 MDA-MB-231、MCF-7 和 BT-474 的生长，而相似的治疗剂量对正常人 MCF10A 细胞的生长没有影响。此外，(-)-油橄榄处理对乳腺癌细胞系中 HGF 诱导的细胞迁移、侵袭和 G1/S 细胞周期进展产生剂量依赖性抑制。此外，发现 (-)-油橄榄醛治疗效果是通过抑制 HGF 诱导的 c-Met 激活及其下游有丝分裂信号通路来介导的。这种生长抑制作用与 EMT 阻断和细胞运动减少有关。体内研究的进一步结果表明，(-)-油橄榄素治疗可抑制无胸腺裸鼠乳腺癌原位模型中的肿瘤细胞生长。总的来说，这项研究的结果表明，(-)-油棘醛是一种有前途的膳食补充剂先导物质，具有用于控制 c-Met 活性异常的恶性肿瘤的治疗用途。
Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (-)-oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (-)-oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (-)-oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (-)-oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (-)-oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.
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影响因子：
50.3
作者：
Cooke VG;LeBleu VS;Keskin D;Khan Z;O'Connell JT;Teng Y;Duncan MB;Xie L;Maeda G;Vong S;Sugimoto H;Rocha RM;Damascena A;Brentani RR;Kalluri R
通讯作者：
Kalluri R
影响因子：
3.5
作者：
Cicerale, Sara;Breslin, Paul A. S.;Keast, Russell S. J.
通讯作者：
Keast, Russell S. J.
影响因子：
5
作者：
Abuznait, Alaa H.;Qosa, Hisham;Kaddoumi, Amal
通讯作者：
Kaddoumi, Amal
影响因子：
64.8
作者：
GIORDANO, S;PONZETTO, C;COMOGLIO, PM
通讯作者：
COMOGLIO, PM
影响因子：
2.7
作者：
Elnagar, Ahmed Y.;Sylvester, Paul W.;El Sayed, Khalid A.
通讯作者：
El Sayed, Khalid A.