Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.
Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.
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DOI：
10.1371/journal.pone.0023395
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shukla Y
中科院分区：
文献类型：
--
作者：
George J;Singh M;Srivastava AK;Bhui K;Roy P;Chaturvedi PK;Shukla Y
天然膳食剂的癌症化学预防因其成本效益和广泛的安全边际而受到相当重视。然而，在临床试验中，单药干预未能带来预期的结果；因此，化学预防药物的组合越来越受欢迎。本研究旨在评价白藜芦醇和红茶多酚（BTP）联合抑制DMBA和TPA诱导的小鼠两阶段皮肤癌的化学预防作用。白藜芦醇/BTP单独治疗可使肿瘤发病率降低~ 67%和~ 75%，而两者在低剂量下联合治疗可使肿瘤发病率更显著地降低~ 89% （p<0.01）。联合用药可显著降低肿瘤体积和数目（p<0.01）。机制研究表明，这种组合抑制与磷酸化丝裂原活化蛋白激酶家族蛋白（细胞外信号调节激酶1/2、c-Jun n末端激酶1/2、p38）的表达减少有关，并增加了皮肤组织/肿瘤中总p53和磷酸化p53 （Ser 15）的表达。通过免疫组织化学检测，白藜芦醇和BTP联合治疗也比单独治疗降低了小鼠皮肤组织/肿瘤中增殖细胞核抗原的表达。此外，组织学和细胞死亡分析也证实白藜芦醇和BTP共同抑制细胞增殖并显著诱导细胞凋亡。综上所述，我们的研究结果首次清楚地说明了白藜芦醇和BTP联合使用比单独使用任何一种药物具有更好的抑制活性，并强调了使用膳食药物开发新的联合治疗/化学预防将更有利于抗癌。这种有希望的组合应该在皮肤和其他癌症的治疗试验中进行检验。
Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP) in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01). This combination also significantly regressed tumor volume and number (p<0.01). Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15) in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.
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DOI：
10.1111/j.1525-1438.2006.00773.x
发表时间：
2007-01-01
影响因子：
4.8
作者：
Baker, J. A.;Boakye, K.;Moysich, K. B.
通讯作者：
Moysich, K. B.
影响因子：
8
作者：
Afaq, F;Ahmad, N;Mukhtar, H
通讯作者：
Mukhtar, H
影响因子：
5
作者：
de Kok, Theo M.;van Breda, Simone G.;Manson, Margaret M.
通讯作者：
Manson, Margaret M.
影响因子：
5.8
作者：
Kundu, Joydeb Kumar;Shin, Young Kee;Surh, Young-Joon
通讯作者：
Surh, Young-Joon
影响因子：
2.4
作者：
Kumi-Diaka, James;Merchant, Kendra;Johnson, Michelle
通讯作者：
Johnson, Michelle