異硫氰酸烯丙酿(allyl isothiocyanate，AITC)，富含於十字花科蔬菜，具化學預防(chemoprevention)及 抗癌作用。本研究探討AITC造成攝護腺癌細胞死亡的機轉，發現AITC可以誘導攝護腺癌細胞株RV1及 PC3 產生細胞自嗤，由微管相關蛋白 1 輕鍵 3-II(microtubule-associated protein 1A/1B-light chain 3-II, LC3-II) 的表現量增加可以確證，其作用呈現時間依存性及劑量依存性。由於抑制細胞自噬可以降低癌細胞存活率 並增加細胞凋亡，故屬於保護性細胞自嗤。誘導細胞自嗤相關的訊息傳遞路徑，包括AMPK(AMP-activated protein kinase)、ERK(extracellular signal-regulated kinases)、JNK(c-Jun N-terminal kinases)、p3 8 (P38 mitogen-activated protein kinases)、beclin-1 以及 mTOR(mammalian target of rapamycin)。彳貞測其石粦酸化蛋白質 發現AMPK、JNK及beclin-1有活化的情形，分別將其抑制後，僅有beclin-1路徑表現出LC3-II表現量減 少的情形。此乃表示是經由becline-1的路徑引起後續作用，這與BITC透過mTOR抑制路徑誘導細胞自嗤 不同。AITC會誘導攝護腺癌細胞產生氧自由基，此一反應不會受到細胞自嗤抑制劑Baf A1(bafilomycin A1) 或細胞〉周亡抑制劑 Z-VAD-FMK(benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone)前處理的影響。本 研究亦發現AITC對正常攝護腺上皮細胞(normal prostate epithelial cell)幾乎沒有傷害，不會產生氧自由基， 也不會誘導細胞自噬或細胞凋亡，因此在臨床應用方面，相對安全。

Allyl isothiocyanate (AITC) is one of the most widely studied phytochemicals with chemopreventive and anti- cancer effect. Our study demonstrates the mechanism of AITC-induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and PC3 cells, judging by the increased level of LC3-II protein in a doseand time-dependent manner. 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, p38 and beclin-1, whereas ERK AMPK, JNK and beclin-1 activation were 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 attenuated autophagy induction, indicating that AITC-induced autophagy occurs through up-regulating beclin-1. AITC also induces ROS generation in prostate cancer cells. Pretreatment with Baf A1 or Z-VAD-FMK in AITC treated prostate cancer cells did not alter the generation of ROS. There are almost no ROS generation, autophagy nor did apoptosis in AITC treat normal prostate epithelial cell. Overall, our data show for the first time that AITC induces protective autophagy in Rv1 and PC3 cells through up-regulation of beclin-1. Our results could potentially contribute to a therapeutic application of AITC in treating prostate cancer.