Bitter melon reduces head and neck squamous cell carcinoma growth by targeting c-Met signaling.
Bitter melon reduces head and neck squamous cell carcinoma growth by targeting c-Met signaling.
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DOI：
10.1371/journal.pone.0078006
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ray RB
中科院分区：
文献类型：
--
作者：
Rajamoorthi A;Shrivastava S;Steele R;Nerurkar P;Gonzalez JG;Crawford S;Varvares M;Ray RB
头颈部鳞状细胞癌（HNSCC）仍然难以治疗，尽管治疗取得了进展，但在过去几年中，总体生存率仅略有提高。因此，迫切需要额外的治疗方式。我们假设用膳食产品如苦瓜提取物（BME）治疗HNSCC细胞调节多种信号传导途径并在临床前模型中使HNSCC肿瘤生长消退。我们观察到HNSCC细胞系中细胞增殖减少。机制研究表明，BME处理HNSCC细胞抑制c-Met信号通路。我们还观察到，BME治疗HNSCC减少了磷酸化Stat 3，c-myc和Mcl-1的表达，c-Met的下游信号分子。此外，HNSCC细胞中的BME处理调节关键细胞周期进展分子的表达，导致细胞生长停止。最后，在携带HNSCC异种移植肿瘤的小鼠中饲喂BME导致肿瘤生长和c-Met表达的抑制。总之，我们的结果表明，BME治疗HNSCC细胞调节多种信号通路，并可能具有治疗HNSCC的治疗潜力。
Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC.
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DOI：
10.1158/1078-0432.ccr-08-3252
发表时间：
2009-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Knowles LM;Stabile LP;Egloff AM;Rothstein ME;Thomas SM;Gubish CT;Lerner EC;Seethala RR;Suzuki S;Quesnelle KM;Morgan S;Ferris RL;Grandis JR;Siegfried JM
通讯作者：
Siegfried JM
DOI：
10.1158/1078-0432.ccr-12-1555
发表时间：
2013-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Stabile LP;He G;Lui VW;Thomas S;Henry C;Gubish CT;Joyce S;Quesnelle KM;Siegfried JM;Grandis JR
通讯作者：
Grandis JR
影响因子：
2.3
作者：
Sahu N;Grandis JR
通讯作者：
Grandis JR
影响因子：
5.7
作者：
Tabata, Keiichi;Hamano, Aoi;Suzuki, Takashi
通讯作者：
Suzuki, Takashi
影响因子：
5.4
作者：
Kanda, Tatsuo;Steele, Robert;Ray, Ratna B.
通讯作者：
Ray, Ratna B.