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

Boonyarat,Chantana; Tantiwatcharakunthon,Mongkhonphan; Takomthong,Pitchayakarn; Yenjai,Chavi; Hayakawa,Yoshihiro; Dejkriengkraikul,Pornngarm; Chaiwiwatrakul,Suchada; Waiwut,Pornthip

doi:10.3892/or.2022.8452

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
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Affiliations: Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand, Natural Products Research Unit, Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand, Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930‑0194, Japan, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand, Department of English, Faculty of Humanities and Social Sciences, Ubon Ratchathani Rajabhat University, Ubon Ratchathani 34000, Thailand
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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