Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells.

Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells.
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DOI:
10.3892/ijo.20.3.631
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发表时间:
2002-03
影响因子:
5.2
通讯作者:
J. Chiao;F. Chung;R. Kancherla;T. Ahmed;A. Mittelman;Conaway Cc
J. Chiao;F. Chung;R. Kancherla;T. Ahmed;A. Mittelman;Conaway Cc
中科院分区:
医学2区
文献类型:
--
作者:
J. Chiao;F. Chung;R. Kancherla;T. Ahmed;A. Mittelman;Conaway Cc

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尽管具体的植物化学物质尚不清楚,但食用十字花科蔬菜与减少前列腺癌发生率之间的关系已被证实。研究了西兰花和其他十字花科蔬菜中作为前体硫代葡萄糖苷存在的萝卜硫素 (SFN) 及其代谢物 N-乙酰半胱氨酸缀合物 (SFN-NAC) 对前列腺癌细胞的影响。使用雄激素依赖性人前列腺癌 LNCaP 细胞系模型对 SFN 和 SFN-NAC 进行分析。通过雄激素受体和前列腺特异性抗原的表达、DNA合成、细胞周期进程、DNA链断裂和半胱天冬酶激活来测定细胞生长和凋亡,以确定效果和机制。首次证明 SFN 和 SFN-NAC 可介导前列腺癌细胞的剂量依赖性细胞凋亡和生长停滞。 Caspases 被激活,并且在凋亡细胞中检测到 DNA 链断裂。磷酸化和去磷酸化雄激素受体的表达以及前列腺特异性抗原的产生减弱。 cyclin D1 的表达和 DNA 合成受​​到抑制,G1 细胞周期受阻,导致细胞密度和生长下降。 SFN 及其代谢物 SFN-NAC 具有相似的诱导生长停滞和细胞凋亡的活性,表明 SFN 的作用在代谢过程中得以维持。 SFN 作为十字花科蔬菜的膳食成分,对预防前列腺癌具有积极作用。
The relation between the consumption of cruciferous vegetables and reduced prostate cancer occurrence has been documented, although the responsible phytochemicals are unknown. The effects of sulforaphane (SFN) which occurs as the precursor glucosinolate in broccoli and other cruciferous vegetables, and its metabolite N-acetylcysteine conjugate (SFN-NAC) on prostate cancer cells were investigated. SFN and SFN-NAC were analyzed with the androgen-dependent human prostate cancer LNCaP cell line model. Cell growth and apoptosis were determined with the expression of androgen receptor and prostate specific antigen, DNA synthesis, cell cycle progression, DNA strand breaks and caspase activation to ascertain the effects and mechanism. SFN and SFN-NAC were demonstrated for the first time to mediate a dose-dependent apoptosis and growth arrest in the prostate cancer cells. Caspases were activated and DNA strand breaks were detected in apoptotic cells. The expression of phosphorylated and dephosphorylated androgen receptors, and the production of prostate specific antigen were attenuated. The expression of cyclin D1 and DNA synthesis were inhibited along with G1 cell cycle block, causing decreased cell density and growth. SFN and its metabolite SFN-NAC have similar activities to induce growth arrest and apoptosis, indicating that the effects of SFN are maintained through the metabolic processes. SFN as a dietary component of cruciferous vegetables active in the prevention of prostate cancer is discussed.