Stella Baliou1, Maria Goulielmaki1, Petros Ioannou2, Christina Cheimonidi3, Ioannis P Trougakos3, Markus Nagl4, Anthony M Kyriakopoulos5, Vassilis Zoumpourlis1. 1. Biomedical Application Unit, Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., 11635 Athens, Greece. 2. Department of Internal Medicine & Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Crete, Greece. 3. Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece. 4. Department of Hygiene, Microbiology and Public Health, Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria. 5. Department of Research and Development, Nasco AD Biotechnology Laboratory, 11 Sachtouri Str, 18536 Piraeus, Greece.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
Entities:
Keywords:
breast cancer; bromamine T; colon cancer; taurine
Authors: Ryan B Corcoran; Hiromichi Ebi; Alexa B Turke; Erin M Coffee; Michiya Nishino; Alexandria P Cogdill; Ronald D Brown; Patricia Della Pelle; Dora Dias-Santagata; Kenneth E Hung; Keith T Flaherty; Adriano Piris; Jennifer A Wargo; Jeffrey Settleman; Mari Mino-Kenudson; Jeffrey A Engelman Journal: Cancer Discov Date: 2012-01-16 Impact factor: 39.397
Authors: S S Bacus; A V Gudkov; M Lowe; L Lyass; Y Yung; A P Komarov; K Keyomarsi; Y Yarden; R Seger Journal: Oncogene Date: 2001-01-11 Impact factor: 9.867
Authors: Lindsey A Torre; Freddie Bray; Rebecca L Siegel; Jacques Ferlay; Joannie Lortet-Tieulent; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2015-02-04 Impact factor: 508.702
Authors: Stella Baliou; Michael Sofopoulos; Maria Goulielmaki; Demetrios A Spandidos; Petros Ioannou; Anthony M Kyriakopoulos; Vassilios Zoumpourlis Journal: Int J Mol Med Date: 2021-02-04 Impact factor: 4.101