Baliou Stella, Goulielmaki Maria, Ioannou Petros, Cheimonidi Christina, Trougakos Ioannis P, Nagl Markus, Kyriakopoulos Anthony M, Zoumpourlis Vassilis
Biomedical Application Unit, Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., 11635 Athens, Greece.
Department of Internal Medicine & Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Crete, Greece.
Cancers (Basel). 2021 Jan 7;13(2):182. doi: 10.3390/cancers13020182.
Taurine (Tau) ameliorates cancer pathogenesis. Researchers have focused on the functional properties of bromamine T (BAT), a stable active bromine molecule. Both N-bromotaurine (TauNHBr) and BAT exert potent anti-inflammatory properties, but the landscape remains obscure concerning the anti-cancer effect of BAT.
We used Crystal Violet, colony formation, flow cytometry and Western blot experiments to evaluate the effect of BAT and Tau on the apoptosis and autophagy of cancer cells. Xenograft experiments were used to determine the in vivo cytotoxicity of either agent.
We demonstrated that both BAT and Tau inhibited the growth of human colon, breast, cervical and skin cancer cell lines. Among them, BAT exerted the greatest cytotoxic effect on both RKO and MDA-MB-468 cells. In particular, BAT increased the phosphorylation of c-Jun N-terminal kinases (JNK½), p38 mitogen-activated protein kinase (MAPK), and extracellular-signal-regulated kinases (ERK½), thereby inducing mitochondrial apoptosis and autophagy in RKO cells. In contrast, Tau exerted its cytotoxic effect by upregulating JNK½ forms, thus triggering mitochondrial apoptosis in RKO cells. Accordingly, colon cancer growth was impaired in vivo.
BAT and Tau exerted their anti-tumor properties through the induction of (i) mitochondrial apoptosis, (ii) the MAPK family, and iii) autophagy, providing novel anti-cancer therapeutic modalities.
牛磺酸(Tau)可改善癌症发病机制。研究人员一直关注稳定的活性溴分子溴胺T(BAT)的功能特性。N-溴代牛磺酸(TauNHBr)和BAT均具有强大的抗炎特性,但关于BAT的抗癌作用,目前尚不清楚。
我们使用结晶紫、集落形成、流式细胞术和蛋白质印迹实验来评估BAT和Tau对癌细胞凋亡和自噬的影响。采用异种移植实验来确定这两种药物的体内细胞毒性。
我们证明,BAT和Tau均能抑制人结肠、乳腺、宫颈和皮肤癌细胞系的生长。其中,BAT对RKO和MDA-MB-468细胞的细胞毒性最大。特别是,BAT增加了c-Jun氨基末端激酶(JNK½)、p38丝裂原活化蛋白激酶(MAPK)和细胞外信号调节激酶(ERK½)的磷酸化,从而诱导RKO细胞发生线粒体凋亡和自噬。相比之下,Tau通过上调JNK½的形式发挥其细胞毒性作用,从而触发RKO细胞的线粒体凋亡。因此,体内结肠癌的生长受到抑制。
BAT和Tau通过诱导(i)线粒体凋亡、(ii)MAPK家族和(iii)自噬发挥其抗肿瘤特性,提供了新的抗癌治疗方式。