Hydroxychavicol, a polyphenol from Piper betle leaf extract, induces cell cycle arrest and apoptosis in TP53-resistant HT-29 colon cancer cells

Rajedadram, Aiysvariyah and Pin, Kar Yong and Ling, Sui Kiong and Yan, See Wan and Looi, Mee Lee (2021) Hydroxychavicol, a polyphenol from Piper betle leaf extract, induces cell cycle arrest and apoptosis in TP53-resistant HT-29 colon cancer cells. Journal of Zhejiang University-SCIENCE B, 22 (2). pp. 112-122. ISSN 1673-1581, DOI https://doi.org/10.1631/jzus.B2000446.

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Abstract

This study aims to elucidate the antiproliferative mechanism of hydroxychavicol (HC). Its effects on cell cycle, apoptosis, and the expression of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK) in HT-29 colon cancer cells were investigated. HC was isolated from Piper betle leaf (PBL) and verified by high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and gas chromatography-mass spectrometry (GC-MS). The cytotoxic effects of the standard drug 5-fluorouracil (5-FU), PBL water extract, and HC on HT-29 cells were measured after 24, 48, and 72 h of treatment. Cell cycle and apoptosis modulation by 5-FU and HC treatments were investigated up to 30 h. Changes in phosphorylated JNK (pJNK) and P38 (pP38) MAPK expression were observed up to 18 h. The half maximal inhibitory concentration (IC50) values of HC (30 mu g/mL) and PBL water extract (380 mu g/mL) were achieved at 24 h, whereas the IC50 of 5-FU (50 mu mol/L) was obtained at 72 h. Cell cycle arrest at the G(0)/G(1) phase in HC-treated cells was observed from 12 h onwards. Higher apoptotic cell death in HC-treated cells compared to 5-FU-treated cells (P<0.05) was observed. High expression of pJNK and pP38 MAPK was observed at 12 h in HC-treated cells, but not in 5-FU-treated HT-29 cells (P<0.05). It is concluded that HC induces cell cycle arrest and apoptosis of HT-29 cells, with these actions possibly mediated by JNK and P38 MAPK.

Item Type: Article
Funders: Taylor's Research Grant Scheme, Malaysia (TRGS/MFS/2/2013/SBS/003)
Uncontrolled Keywords: Piper betle; Hydroxychavicol (HC); Cell cycle; Apoptosis; c-Jun N-terminal kinase (JNK); P38 mitogen-activated protein kinase (MAPK)
Subjects: Q Science > QD Chemistry
Q Science > QR Microbiology
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 17 Jun 2022 08:16
Last Modified: 17 Jun 2022 08:16
URI: http://eprints.um.edu.my/id/eprint/27945

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