TY - JOUR
T1 - Neuroprotective and anticancer effects of 7‑Methoxyheptaphylline via the TAK1 pathway
AU - Boonyarat, Chantana
AU - Tantiwatcharakunthon, Mongkhonphan
AU - Takomthong, Pitchayakarn
AU - Yenjai, Chavi
AU - Hayakawa, Yoshihiro
AU - Dejkriengkraikul, Pornngarm
AU - Chaiwiwatrakul, Suchada
AU - Waiwut, Pornthip
N1 - Publisher Copyright:
© 2023 Spandidos Publications. All rights reserved.
PY - 2023/1
Y1 - 2023/1
N2 - 7‑Methoxyheptaphylline (7‑MH) is a carbazole extracted from Clausena harmandiana, a medicinal plant that is used to treat headaches and stomachaches. The aim of the present study was to examine the neuroprotective effects and anticancer activity of 7‑MH. Cell death was assessed using an MTT assay and flow cytometry. The expression of apoptosis‑related proteins was determined by western blot analysis. An animal model was used to test anti‑metastasis. The interactions between 7‑MH and the molecular target were observed using molecular docking. The results revealed that 7‑MH provided protection against hydrogen peroxide (H2O2)‑induced neuronal cell death. In cancer cells, 7‑MH induced SH‑SY5Y, 4T1, HT29, HepG2, and LNCaP cell death. 7‑MH inhibited metastasis of HT29 cells in vitro and 4T1‑Luc cells in vitro and in vivo. 7‑MH inhibited proteins, including P‑glycogen synthase kinase (GSK)‑3, and cleaved caspase‑3, but it activated anti‑apoptotic proteins in H2O2‑induced SH‑SY5Y cell death. By contrast, 7‑MH activated the cleaving of caspase‑3 and GSK‑3, but it suppressed anti‑apoptotic proteins in SH‑SY5Y cells. 7‑MH reduced the levels of NF‑κB and STAT3 in 4T1 cells; phospho‑p65, Erk, and MAPK13 in LNCaP cells; and phospho‑Erk and matrix metalloproteinase‑9 in HT29 cells. Molecular docking analysis showed that 7‑MH targets TAK1 kinase. The present study indicated that 7‑MH induced apoptosis of cancer cells and provided protection against H2O2‑induced neuron cell death via TAK1 kinase.
AB - 7‑Methoxyheptaphylline (7‑MH) is a carbazole extracted from Clausena harmandiana, a medicinal plant that is used to treat headaches and stomachaches. The aim of the present study was to examine the neuroprotective effects and anticancer activity of 7‑MH. Cell death was assessed using an MTT assay and flow cytometry. The expression of apoptosis‑related proteins was determined by western blot analysis. An animal model was used to test anti‑metastasis. The interactions between 7‑MH and the molecular target were observed using molecular docking. The results revealed that 7‑MH provided protection against hydrogen peroxide (H2O2)‑induced neuronal cell death. In cancer cells, 7‑MH induced SH‑SY5Y, 4T1, HT29, HepG2, and LNCaP cell death. 7‑MH inhibited metastasis of HT29 cells in vitro and 4T1‑Luc cells in vitro and in vivo. 7‑MH inhibited proteins, including P‑glycogen synthase kinase (GSK)‑3, and cleaved caspase‑3, but it activated anti‑apoptotic proteins in H2O2‑induced SH‑SY5Y cell death. By contrast, 7‑MH activated the cleaving of caspase‑3 and GSK‑3, but it suppressed anti‑apoptotic proteins in SH‑SY5Y cells. 7‑MH reduced the levels of NF‑κB and STAT3 in 4T1 cells; phospho‑p65, Erk, and MAPK13 in LNCaP cells; and phospho‑Erk and matrix metalloproteinase‑9 in HT29 cells. Molecular docking analysis showed that 7‑MH targets TAK1 kinase. The present study indicated that 7‑MH induced apoptosis of cancer cells and provided protection against H2O2‑induced neuron cell death via TAK1 kinase.
KW - 7‑methoxyheptaphylline
KW - Clausena harmandiana
KW - TGF‑β‑activated kinase 1
KW - apoptosis
KW - cancer
KW - glycogen synthase kinase‑3
KW - neuron cells
UR - http://www.scopus.com/inward/record.url?scp=85142504851&partnerID=8YFLogxK
U2 - 10.3892/or.2022.8452
DO - 10.3892/or.2022.8452
M3 - 学術論文
C2 - 36416312
AN - SCOPUS:85142504851
SN - 1021-335X
VL - 49
JO - Oncology Reports
JF - Oncology Reports
IS - 1
M1 - 15
ER -
