Trichosanthin suppresses HeLa cell proliferation through inhibition of the PKC/MAPK signaling pathway
Trichosanthin suppresses HeLa cell proliferation through inhibition of the PKC/MAPK signaling pathway
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DOI：
10.1007/s10565-008-9102-x
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发表时间：
2009-10
影响因子：
6.1
通讯作者：
Ping Wang;Lili Chen;Hui Yan;Jicheng Li
中科院分区：
文献类型：
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作者：
Ping Wang;Lili Chen;Hui Yan;Jicheng Li
天花粉蛋白具有广泛的生物活性和药理活性，包括抗肿瘤活性。我们以前的研究表明TCS通过激活凋亡途径抑制HeLa细胞增殖。特别是，转录因子cAMP反应元件结合（CREB）蛋白在凋亡HeLa细胞中起关键作用。然而，没有信息，到目前为止，是有关的信号通路参与抑制细胞增殖诱导的TCS。结果表明，TCS处理后，PKA和PKC活性均显著降低。然而，PKA活性的特异性抑制剂不能影响TCS诱导的HeLa细胞增殖抑制，即使在cAMP激动剂的存在下。相反，PKC激活剂/抑制剂显著减弱/增强TCS对细胞增殖的抑制作用。特别是，cAMP激动剂对细胞增殖的逆转作用部分被PKC、ERK 1/2和p38 MAPK阻断剂所阻断。与这些结果一致，cAMP激动剂对CREB磷酸化的逆转作用被这些激酶的抑制剂显著降低，但PKA抑制剂没有。结果表明，TCS通过抑制PKC/MAPK信号通路抑制HeLa细胞增殖。
Trichosanthin (TCS) possesses a broad spectrum of biological and pharmacological activities, including anti-tumor activities. Our previous studies have shown that TCS inhibits HeLa cell proliferation by activating the apoptotic pathway. In particular, the transcriptional factor cAMP response element binding (CREB) protein plays a pivotal role in apoptotic HeLa cells. However, no information, to date, is available about the signaling pathways involved in the inhibition of cell proliferation induced by TCS. The present study showed that PKA and PKC activities were significantly inhibited by TCS treatment. However, specific inhibitor of PKA activity failed to affect the inhibition of HeLa cell proliferation induced by TCS, even in the presence of cAMP agonists. In contrast, PKC activator/inhibitor significantly attenuated/enhanced the inhibitory effect of TCS on cell proliferation. In particular, the reversed effect of cAMP agonist on cell proliferation was partly prevented by PKC, ERK1/2, and p38 MAPK blockade. Consistent with these results, the reversed effect of cAMP agonists on CREB phosphorylation was significantly decreased by inhibitors of these kinases, but not PKA inhibitor. Therefore, our results suggested that HeLa cell proliferation was inhibited by TCS via suppression of PKC/MAPK signaling pathway.