Open Access

Neuroprotective and anticancer effects of 7‑Methoxyheptaphylline via the TAK1 pathway

  • Authors:
    • Chantana Boonyarat
    • Mongkhonphan Tantiwatcharakunthon
    • Pitchayakarn Takomthong
    • Chavi Yenjai
    • Yoshihiro Hayakawa
    • Pornngarm Dejkriengkraikul
    • Suchada Chaiwiwatrakul
    • Pornthip Waiwut
  • View Affiliations

  • Published online on: November 23, 2022     https://doi.org/10.3892/or.2022.8452
  • Article Number: 15
  • Copyright: © Boonyarat et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

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.

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January-2023
Volume 49 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Boonyarat C, Tantiwatcharakunthon M, Takomthong P, Yenjai C, Hayakawa Y, Dejkriengkraikul P, Chaiwiwatrakul S and Waiwut P: Neuroprotective and anticancer effects of 7‑Methoxyheptaphylline via the TAK1 pathway. Oncol Rep 49: 15, 2023
APA
Boonyarat, C., Tantiwatcharakunthon, M., Takomthong, P., Yenjai, C., Hayakawa, Y., Dejkriengkraikul, P. ... Waiwut, P. (2023). Neuroprotective and anticancer effects of 7‑Methoxyheptaphylline via the TAK1 pathway. Oncology Reports, 49, 15. https://doi.org/10.3892/or.2022.8452
MLA
Boonyarat, C., Tantiwatcharakunthon, M., Takomthong, P., Yenjai, C., Hayakawa, Y., Dejkriengkraikul, P., Chaiwiwatrakul, S., Waiwut, P."Neuroprotective and anticancer effects of 7‑Methoxyheptaphylline via the TAK1 pathway". Oncology Reports 49.1 (2023): 15.
Chicago
Boonyarat, C., Tantiwatcharakunthon, M., Takomthong, P., Yenjai, C., Hayakawa, Y., Dejkriengkraikul, P., Chaiwiwatrakul, S., Waiwut, P."Neuroprotective and anticancer effects of 7‑Methoxyheptaphylline via the TAK1 pathway". Oncology Reports 49, no. 1 (2023): 15. https://doi.org/10.3892/or.2022.8452