Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells.
Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells.
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DOI：
10.1038/sj.bjc.6603595
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发表时间：
2007-02-26
影响因子：
8.8
通讯作者：
Chen, C-Y
中科院分区：
文献类型：
--
作者：
Zhu, T.;Guo, J.;Collins, L.;Kelly, J.;Xiao, Z. J.;Kim, S-H;Chen, C-Y
已知从林菇（Phellinus linteus）中提取的多糖具有抗肿瘤活性。我们之前已经证明，高剂量的PL使小鼠或人肺癌细胞易发生凋亡。然而，pl介导的细胞凋亡的分子机制尚未被充分探讨。在本研究中，我们证明了表达雄激素受体（AR）的LNCaP细胞在高剂量PL处理下高度易发生凋亡。在此过程中，caspase 8及其下游效应物（如BID）以及内质网络应激相关的凋亡信号被激活。相反，在同样的处理后，PC3细胞（缺乏AR）发生了适量的凋亡，这并不激活er介导的凋亡信号传导。我们还发现，在pl诱导的凋亡过程中，caspase 2在LNCaP细胞中被诱导，而在PC3细胞中不被诱导。然而，表达突变AR的LNCaP细胞或经过caspase 2抑制剂处理的LNCaP细胞可阻断内质网应激诱导的凋亡信号。这些细胞诱导凋亡的程度与PC3细胞中发生的情况相当。数据表明，高剂量的PL激活ar依赖性和独立的凋亡通路。我们的研究还表明，caspase 2是确定前列腺癌细胞对pl诱导的凋亡易感性的关键靶点。
It is known that polysaccharides extracted from the Phellinus linteus (PL) mushroom possess antitumour activity. We previously have demonstrated that high doses of PL render murine or human lung cancer cells susceptible to apoptosis. However, the molecular mechanisms of PL-mediated apoptosis have not been fully explored. In this study, we demonstrate that LNCaP cells expressing the androgen receptor (AR) are highly susceptible to apoptosis in response to treatment with high doses of PL. In this process, caspase 8 and its downstream effectors (such as BID), as well as ER stress-related, apoptotic signalling, are activated. In contrast, a moderate amount of apoptosis occurs in PC3 cells (that lack AR) after the same treatment, which does not activate ER-mediated apoptotic signalling. We also show that, in the process of PL-induced apoptosis, caspase 2 is induced in LNCaP cells, but not in PC3 cells. However, LNCaP cells that express a mutated AR or LNCaP cells treated with a caspase 2 inhibitor blocked ER stress-induced apoptotic signals. The magnitudes of the induction of apoptosis in these cells are comparable with what occurred in the PC3 cells. The data demonstrate that high doses of PL activate the AR-dependent and independent apoptotic pathways. Our study also suggests that caspase 2 is a key target in the determination of the susceptibility of prostate cancer cells to PL-induced apoptosis.
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