School of Biosciences, Taylor's University, Lakeside Campus, 47500 Subang Jaya, Malaysia.
Forest Research Institute Malaysia, 52109 Kepong, Malaysia.
J Zhejiang Univ Sci B. 2021 Feb 15;22(2):112-122. doi: 10.1631/jzus.B2000446.
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 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 (IC) values of HC (30 μg/mL) and PBL water extract (380 μg/mL) were achieved at 24 h, whereas the IC of 5-FU (50 μmol/L) was obtained at 72 h. Cell cycle arrest at the G/G 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 (<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 (<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.
本研究旨在阐明羟基查尔酮（HC）的抗增殖机制。研究了其对 HT-29 结肠癌细胞周期、细胞凋亡以及 c-Jun N-末端激酶（JNK）和 P38 丝裂原活化蛋白激酶（MAPK）表达的影响。通过高效液相色谱（HPLC）、核磁共振（NMR）和气相色谱-质谱联用（GC-MS）从叶片（PBL）中分离并验证了 HC。在 24、48 和 72 h 处理后，测量了标准药物 5-氟尿嘧啶（5-FU）、PBL 水提取物和 HC 对 HT-29 细胞的细胞毒性作用。研究了 5-FU 和 HC 处理对细胞周期和细胞凋亡的调节作用，最长可达 30 h。观察到磷酸化 JNK（pJNK）和 P38（pP38）MAPK 表达的变化最长可达 18 h。HC（30 μg/mL）和 PBL 水提取物（380 μg/mL）的半最大抑制浓度（IC）值在 24 h 时达到，而 5-FU（50 μmol/L）的 IC 值在 72 h 时达到。HC 处理的细胞中从 12 h 开始观察到细胞周期阻滞在 G1/G 期。与 5-FU 处理的细胞相比，HC 处理的细胞中观察到更高的细胞凋亡死亡（<0.05）。在 HC 处理的细胞中，在 12 h 时观察到 JNK 和 P38 MAPK 的高表达，但在 5-FU 处理的 HT-29 细胞中未观察到（<0.05）。结论：HC 诱导 HT-29 细胞的细胞周期阻滞和凋亡，这些作用可能由 JNK 和 P38 MAPK 介导。
