4-Methylcatechol-induced oxidative stress induces intrinsic apoptotic pathway in metastatic melanoma cells.
4-Methylcatechol-induced oxidative stress induces intrinsic apoptotic pathway in metastatic melanoma cells.
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DOI：
10.1016/j.bcp.2011.03.005
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发表时间：
2011-05-15
影响因子：
5.8
通讯作者：
Ghosh R
中科院分区：
文献类型：
--
作者：
Payton F;Bose R;Alworth WL;Kumar AP;Ghosh R
与厚黑色素瘤（> 4 mm）相关的死亡率稳步上升。虽然对这种疾病的生物学的理解已经有所改善，但晚期转移性黑色素瘤患者的有效治疗策略仍然难以捉摸。因此，需要对具有治疗潜力的药物进行更深入的测试，以提高转移性恶性黑色素瘤患者的生存率。我们已经测试了4-甲基儿茶酚的能力，槲皮素的代谢产物;一种天然存在的化合物，通常存在于各种水果中，具有抗黑色素瘤的潜力。我们的研究结果表明，4-甲基儿茶酚抑制黑色素瘤细胞在文化的增殖，而不影响正常人表皮黑色素细胞的生长。此外，转移性黑素瘤细胞在软琼脂上形成集落的能力也受到抑制。4-甲基儿茶酚使细胞聚集于G2/M期，诱导细胞凋亡。4-甲基儿茶酚处理后，活性氧增加，导致细胞凋亡，通过内在线粒体途径。治疗还抑制了Akt介导的细胞存活，Akt是黑色素瘤细胞存活的关键因素。综上所述，我们的研究结果表明，4-甲基儿茶酚对转移性恶性黑色素瘤细胞具有细胞毒性，同时保留正常黑色素细胞，并应进一步测试作为一个潜在的候选药物恶性黑色素瘤。
There has been a steady rise in fatalities associated with thick melanomas (>4mm). Although understanding of the biology of the disease has improved, effective treatment strategies for patients with advanced metastatic melanoma remain elusive. Therefore, more intensive testing of agents with therapeutic potential are needed to improve survival of patients with metastatic malignant melanoma. We have tested the ability of 4-methylcatechol, a metabolite of quercetin; a naturally occurring compound that is commonly found in a variety of fruits for its potential as an anti-melanoma agent. Our results show that 4-methylcatechol inhibits proliferation of melanoma cells in culture while not affecting the growth of normal human epidermal melanocytes. Further, the ability of metastatic melanoma cells to form colonies on soft agar was also inhibited. 4-methylcatechol caused the accumulation of cells in G2/M phase of the cell cycle and induced apoptosis. There was an increase in reactive oxygen species following treatment with 4-methylcatechol that led to apoptosis through the intrinsic mitochondrial pathway. Treatment also inhibited cell survival mediated by Akt, a key player in melanoma cell survival. Taken together our results suggest that 4-methylcatechol exhibits cytotoxicity towards metastatic malignant melanoma cells while sparing normal melanocytes and should be tested further as a potential drug candidate for malignant melanoma.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
6.1
作者：
Häkkinen, SH;Kärenlampi, SO;Törrönen, AR
通讯作者：
Törrönen, AR
影响因子：
4.3
作者：
Brisdelli, Fabrizia;Coccia, Cristina;Bozzi, Argante
通讯作者：
Bozzi, Argante
影响因子：
4.7
作者：
Chen, Wenshu;Wang, Xia;Lin, Yong
通讯作者：
Lin, Yong
影响因子：
45.3
作者：
O'Day, Steven;Gonzalez, Rene;Jacobson, Eric
通讯作者：
Jacobson, Eric