TY - JOUR
T1 - 2,3,5,6-Tetramethylpyrazine Targets Epithelial-Mesenchymal Transition by Abrogating Manganese Superoxide Dismutase Expression and TGFβ-Driven Signaling Cascades in Colon Cancer Cells
AU - Jung, Young Yun
AU - Mohan, Chakrabhavi Dhananjaya
AU - Eng, Huiyan
AU - Narula, Acharan S.
AU - Namjoshi, Ojas A.
AU - Blough, Bruce E.
AU - Rangappa, Kanchugarakoppal S.
AU - Sethi, Gautam
AU - Kumar, Alan Prem
AU - Ahn, Kwang Seok
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7
Y1 - 2022/7
N2 - Epithelial-mesenchymal transition (EMT) is a crucial process in which the polarized epithelial cells acquire the properties of mesenchymal cells and gain invasive properties. We have previously demonstrated that manganese superoxide dismutase (MnSOD) can regulate the EMT phenotype by modulating the intracellular reactive oxygen species. In this report, we have demonstrated the EMT-suppressive effects of 2,3,5,6-Tetramethylpyrazine (TMP, an alkaloid isolated from Chuanxiong) in colon cancer cells. TMP suppressed the expression of MnSOD, fibronectin, vimentin, MMP-9, and N-cadherin with a parallel elevation of occludin and E-cadherin in unstimulated and TGFβ-stimulated cells. Functionally, TMP treatment reduced the proliferation, migration, and invasion of colon cancer cells. TMP treatment also modulated constitutive activated as well as TGFβ-stimulated PI3K/Akt/mTOR, Wnt/GSK3/β-catenin, and MAPK signaling pathways. TMP also inhibited the EMT program in the colon cancer cells-transfected with pcDNA3-MnSOD through modulation of MnSOD, EMT-related proteins, and oncogenic pathways. Overall, these data indicated that TMP may inhibit the EMT program through MnSOD-mediated abrogation of multiple signaling events in colon cancer cells.
AB - Epithelial-mesenchymal transition (EMT) is a crucial process in which the polarized epithelial cells acquire the properties of mesenchymal cells and gain invasive properties. We have previously demonstrated that manganese superoxide dismutase (MnSOD) can regulate the EMT phenotype by modulating the intracellular reactive oxygen species. In this report, we have demonstrated the EMT-suppressive effects of 2,3,5,6-Tetramethylpyrazine (TMP, an alkaloid isolated from Chuanxiong) in colon cancer cells. TMP suppressed the expression of MnSOD, fibronectin, vimentin, MMP-9, and N-cadherin with a parallel elevation of occludin and E-cadherin in unstimulated and TGFβ-stimulated cells. Functionally, TMP treatment reduced the proliferation, migration, and invasion of colon cancer cells. TMP treatment also modulated constitutive activated as well as TGFβ-stimulated PI3K/Akt/mTOR, Wnt/GSK3/β-catenin, and MAPK signaling pathways. TMP also inhibited the EMT program in the colon cancer cells-transfected with pcDNA3-MnSOD through modulation of MnSOD, EMT-related proteins, and oncogenic pathways. Overall, these data indicated that TMP may inhibit the EMT program through MnSOD-mediated abrogation of multiple signaling events in colon cancer cells.
KW - MnSOD
KW - TGFβ signaling
KW - Tetramethylpyrazine
KW - epithelial-mesenchymal transition
UR - http://www.scopus.com/inward/record.url?scp=85132784860&partnerID=8YFLogxK
U2 - 10.3390/biom12070891
DO - 10.3390/biom12070891
M3 - Article
C2 - 35883447
AN - SCOPUS:85132784860
SN - 2218-273X
VL - 12
JO - Biomolecules
JF - Biomolecules
IS - 7
M1 - 891
ER -
