Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in Human Prostate Cancer Cells
Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in Human Prostate Cancer Cells
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DOI：
10.1142/s0192415x18500830
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发表时间：
2018-01-01
影响因子：
5.7
通讯作者：
Hwang, Thomas I-Sheng
中科院分区：
文献类型：
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作者：
Chen, Hung-En;Lin, Ji-Fan;Hwang, Thomas I-Sheng
异硫氰酸烯丙酯 (AITC) 是研究最广泛的植物化学物质之一，可抑制人类前列腺癌细胞的存活，同时对正常前列腺上皮细胞的影响最小。我们的研究证明了 AITC 诱导前列腺癌细胞死亡的机制。从 LC3-II 蛋白水平升高来看，AITC 会在 RV1 和 PC3 细胞中诱导自噬，且呈剂量和时间依赖性，但不会在正常前列腺上皮细胞 (PrEC) 中诱导自噬。 AITC 处理细胞中自噬的抑制降低了细胞活力并增强了细胞凋亡，表明自噬发挥了保护作用。 ATIC 处理的细胞中激活了多种途径。我们检测了mTOR、ERK、AMPK、JNK和p38的磷酸化形式，并且还检测了ERK AMPK和JNK激活。然而，通过特定抑制剂预处理来抑制 AITC 激活的 ERK、AMPK 和 JNK 并不会改变自噬诱导。最后，在 AITC 处理的细胞中检测到 beclin-1 表达增加，并且抑制 AITC 诱导的 beclin-1 会减弱自噬诱导，表明 AITC 诱导的自噬是通过上调 beclin-1 发生的。总体而言，我们的数据首次表明 AITC 通过上调 beclin-1 在 Rv1 和 PC3 细胞中诱导保护性自噬。我们的结果可能有助于 AITC 在前列腺癌患者中的治疗应用。
Allyl isothiocyanate (AITC), one of the most widely studied phytochemicals, inhibits the survival of human prostate cancer cells while minimally affecting normal prostate epithelial cells. Our study demonstrates the mechanism of AITC-induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and PC3 cells, judging from the increased level of LC3-II protein in a dose- and time-dependent manner, but not in the normal prostate epithelial cell (PrEC). Inhibition of autophagy in AITC-treated cells decreased cell viability and enhanced apoptosis, suggesting that the autophagy played a protective role. There are several pathways activated in ATIC-treated cells. We detected the phosphorylation forms of mTOR, ERK, AMPK, JNK and p38, and ERK AMPK and JNK activation were also detected. However, inhibition of AITC-activated ERK, AMPK and JNK by pre-treatment of specific inhibitors did not alter autophagy induction. Finally, increased beclin-1 expression was detected in AITC-treated cells, and inhibition of AITC-induced beclin-1 attanuated autophagy induction, indicating that AITC-induced autophagy occurs through upregulating beclin-1. Overall, our data show for the first time that AITC induces protective autophagy in Rv1 and PC3 cells through upregulation of beclin-1. Our results could potentially contribute to a therapeutic application of AITC in prostate cancer patients.