Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia. Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain.
Curr Pharm Des. 2012;18(12):1663-76. doi: 10.2174/138161212799958549.
Triterpenes have been reported to induce cell death. One relevant group of this family of compounds is cucurbitacins, which have been studied as inducers of apoptosis in various cancer cell lines. The most significant mechanisms with regard to the apoptotic effects of cucurbitacins are their ability to modify transcriptional activities via nuclear factors or genes and their capability to activate or inhibit pro- or anti-apoptotic proteins. Still, while the majority of studies on these compounds have dealt with their apoptotic effects on cancer cell lines, several research groups have also explored their anti-inflammatory activities. In general, cucurbitacins are considered to be selective inhibitors of the JAK/STAT pathways; however, other mechanisms may be implicated in their apoptotic effects, including the MAPK pathway (known to be important for cancer cell proliferation and survival), PARP cleavage, expression of active caspase-3, decreased pSTAT3 and JAK3 levels, as well as decreases in various downstream STAT3 targets such as Mcl-1, Bcl-2, Bcl-xL, and cyclin D3, all of which are implicated in apoptosis and the cell cycle. Taking all these effects into account, cucurbitacins may prove useful in the treatment of different kinds of cancers, especially when used with other cytostatic agents.
三萜类化合物已被报道可诱导细胞死亡。这类化合物中有一种相关的化合物是葫芦素，它已被研究作为各种癌细胞系凋亡的诱导剂。关于葫芦素的凋亡作用，最重要的机制是它们通过核因子或基因改变转录活性的能力，以及它们激活或抑制促凋亡或抗凋亡蛋白的能力。尽管大多数关于这些化合物的研究都涉及它们对癌细胞系的凋亡作用，但一些研究小组也探索了它们的抗炎活性。一般来说，葫芦素被认为是 JAK/STAT 途径的选择性抑制剂；然而，其他机制可能与它们的凋亡作用有关，包括 MAPK 途径（已知对癌细胞增殖和存活很重要）、PARP 切割、活性 caspase-3 的表达、pSTAT3 和 JAK3 水平的降低，以及各种下游 STAT3 靶标如 Mcl-1、Bcl-2、Bcl-xL 和 cyclin D3 的减少，所有这些都与凋亡和细胞周期有关。考虑到所有这些影响，葫芦素在治疗不同类型的癌症方面可能很有用，特别是与其他细胞抑制剂一起使用时。
