Bioactive phytochemical proanthocyanidins inhibit growth of head and neck squamous cell carcinoma cells by targeting multiple signaling molecules.
Bioactive phytochemical proanthocyanidins inhibit growth of head and neck squamous cell carcinoma cells by targeting multiple signaling molecules.
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DOI：
10.1371/journal.pone.0046404
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Katiyar SK
中科院分区：
文献类型：
--
作者：
Prasad R;Katiyar SK
尽管手术和药物治疗取得了进展，但在过去的30年中，头颈部鳞状细胞癌（HNSCC）的生存率约为50%。因此，HNSCC的管理需要替代策略。在这里，我们报告的化疗效果的原花青素对HNSCC细胞在体外和体内模型。用葡萄籽原花青素（GSPs）处理来自不同亚部位的人HNSCC细胞系，如口腔（SCC 1）、喉（SCC 5）、舌（OSC 19）和咽（FaDu），以剂量和时间依赖性方式降低其细胞活力并诱导细胞死亡。GSPs诱导的细胞活力抑制与以下因素有关：（i）G1期阻滞，（ii）抑制细胞周期蛋白（细胞周期蛋白D1和细胞周期蛋白D2）和细胞周期蛋白依赖性激酶（Cdk）的表达，（iii）增加Cdk抑制蛋白（Cip 1/p21，Kip 1/p27）的表达，增强Cdk抑制剂与Cdks的结合，以及下调E2 F转录因子。GSPs显著（P<0.05 - 0.001）增加了SCC 1和OSC 19细胞的凋亡，诱导Bax，降低Bcl-2的表达，激活caspase-3。GSP还降低了表皮生长因子受体（EGFR）的表达，用厄洛替尼（一种EGFR靶向小分子酪氨酸激酶抑制剂）处理SCC 1细胞，显著（P<0.05 - 0.001）降低了细胞活力，增加了细胞死亡。GSP的饮食管理（0.5%，w/w）补充AIN 76 A对照饮食抑制无胸腺裸鼠中SCC 1肿瘤异种移植物的生长，这与以下相关：（i）抑制细胞增殖，（ii）诱导肿瘤异种移植细胞的凋亡，（iii）降低细胞周期蛋白和Cdks的表达，（iv）降低EGFR的表达，和（v）肿瘤异种移植物样品中Cip 1/p21和Kip 1/p27蛋白表达增加及其与Cdks结合增加。总之，这些结果表明，GSPs可能是头颈部鳞状细胞癌治疗的一个有前途的候选者。
Despite advances in surgical and medical therapies, approximate 50% survival rate of head and neck squamous cell carcinoma (HNSCC) has had marginal improvement in the last 30 years. Therefore, alternative strategies are required for the management of HNSCC. Here, we report the chemotherapeutic effect of proanthocyanidins on HNSCC cells using in vitro and in vivo models. Treatment of human HNSCC cell lines from different sub-sites, such as oral cavity (SCC1), larynx (SCC5), tongue (OSC19) and pharynx (FaDu), with grape seed proanthocyanidins (GSPs) reduced their cell viability and induced cell death in a dose- and time-dependent manner. GSPs induced inhibition of cell viability was associated with: (i) G1-phase arrest, (ii) inhibition of expressions of cyclins (cyclin D1 and Cyclin D2) and cyclin-dependent kinases (Cdk), (iii) increased expression of the Cdk inhibitory proteins (Cip1/p21, Kip1/p27), enhanced binding of Cdk inhibitors to Cdks, and downregulation of E2F transcription factor. GSPs significantly (P<0.05−0.001) increased apoptosis of SCC1 and OSC19 cells with induction of Bax, reduced expression of Bcl-2, and activation of caspase-3. GSPs also reduced the expression of epidermal growth factor receptor (EGFR), and treatment of SCC1 cells with erlotinib, an EGFR-targeting small molecule tyrosine kinase inhibitor, significantly (P<0.05−0.001) reduced cell viability and increased cell death. Dietary administration of GSPs (0.5%, w/w) in supplementation with AIN76A control diet inhibited the growth of SCC1 tumor xenografts in athymic nude mice, which was associated with: (i) inhibition of cell proliferation, (ii) induction of apoptosis of tumor xenograft cells, (iii) decreased expression of cyclins and Cdks, (iv) decreased expression of EGFR, and (v) increased expression of Cip1/p21 and Kip1/p27 proteins and their increased binding to Cdks in tumor xenograft samples. Together, these results suggest that GSPs may be a promising candidate for head and neck squamous cell carcinoma therapy.
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影响因子：
4.7
作者：
Mantena, Sudheer K.;Baliga, Manjeshwar S.;Katiyar, Santosh K.
通讯作者：
Katiyar, Santosh K.
影响因子：
3.3
作者：
Leon, X;Quer, M;del Prado Venegas, M
通讯作者：
del Prado Venegas, M
DOI：
10.1002/hed.1049
发表时间：
2001-05-01
影响因子：
2.9
作者：
Epstein, JB;Robertson, M;Stevenson-Moore, P
通讯作者：
Stevenson-Moore, P
影响因子：
4.6
作者：
Bock, Jonathan M.;Menon, Sarita G.;Trask, Douglas K.
通讯作者：
Trask, Douglas K.
影响因子：
10.3
作者：
He, YK;Zeng, Q;Grandis, JR
通讯作者：
Grandis, JR