The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor
The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor
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DOI：
10.3390/ijms20215384
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Avery, Vicky M.
中科院分区：
文献类型：
--
作者：
Carrasco-Pozo, Catalina;Kah Ni Tan;Avery, Vicky M.
雄激素受体（AR）刺激物，如雄激素和Tip 60，在前列腺癌发生中起关键作用，因为雄激素受体信号传导对于前列腺的生长和转化至关重要。此外，雄激素和Tip 60促进HIF-1 α激活，通过增加糖酵解参与代谢重编程，这是癌症发生和发展的标志。在这项研究中，我们评估了雄激素和Tip 60刺激在AR通路激活和HIF-1 α稳定化中的作用，在雄激素敏感的LNCaP细胞中的增殖和细胞代谢方面。还讨论了生物活性化合物萝卜硫素和辣椒素对这些刺激物导致致癌特征的影响的保护作用。萝卜硫素和辣椒素降低核AR，前列腺特异性抗原和Bcl-XL水平，并在LNCaP细胞中由雄激素和Tip 60诱导的细胞增殖。这些生物活性化合物阻止了糖酵解、己糖激酶和丙酮酸激酶活性的增加，并降低了LNCaP细胞中由雄激素和Tip 60诱导的HIF-1 α稳定性。萝卜硫素和辣椒素对前列腺癌的保护作用可能依赖于抑制Tip 60、AR和HIF-1 α效应的机制。
Androgen receptor (AR) stimulators, such as androgen and Tip60, play a pivotal role in prostatic carcinogenesis as androgen receptor signaling is critical for the growth and transformation of the prostate gland. Moreover, androgen and Tip60 promotes HIF-1 alpha activation, involved in metabolic reprogramming by increasing glycolysis, a hallmark in cancer initiation and development. In this study we evaluated the effect of androgen and Tip60 stimulus in AR pathway activation and HIF-1 alpha stabilization, in terms of proliferation and cell metabolism in androgen-sensitive LNCaP cells. The protective role of the bioactive compounds sulforaphane and capsaicin against the effect of these stimuli leading to pro-carcinogenic features was also addressed. Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells. These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1 alpha stabilization induced by androgen and Tip60 in LNCaP cells. The protective role of sulforaphane and capsaicin on prostate cancer may rely on mechanisms involving the inhibition of Tip60, AR and HIF-1 alpha effects.