Moakmamern Sirinya, Rueankham Lapamas, Viriyaadhammaa Natsima, Panyakham Kittikawin, Khakhai Natnicha, Khamphikham Pinyaphat, Duangmano Suwit, Okonogi Siriporn, Chiampanichayakul Sawitree, Anuchapreeda Songyot
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Biology (Basel). 2025 Aug 21;14(8):1098. doi: 10.3390/biology14081098.
The c-Myc protein, a key regulator of cell proliferation, growth, and apoptosis in B-cell lymphocytes, is frequently dysregulated in Burkitt's lymphoma. Zingiberaceae plants-galangal (), black turmeric (), black ginger (), phlai lueang (), and phlai dum ()-are traditionally used as herbal remedies and may serve as natural anti-lymphoma agents. In this study, extracts from these five plants were screened for cytotoxicity against Raji and Daudi lymphoma cell lines and compared with their effects on normal peripheral blood mononuclear cells (PBMCs). Galangal extract exhibited the strongest cytotoxic effects on lymphoma cells. Its major bioactive compounds, galangin and 1'-acetoxychavicol acetate (ACA), showed selective cytotoxicity, with ACA being more potent. ACA significantly suppressed both c-Myc and phosphorylated c-Myc (p-c-Myc) protein levels and induced dose-dependent apoptosis in lymphoma cells. Cell cycle analysis revealed arrest at specific phases, supporting its anti-proliferative action. Furthermore, network pharmacology and pathway enrichment analyses implicated ACA in the modulation of oncogenic PI3K-Akt and MAPK pathways. These findings highlight ACA as a promising plant-derived therapeutic candidate for lymphoma, acting through c-Myc suppression, cell cycle arrest, and apoptosis induction.
c-Myc蛋白是B淋巴细胞中细胞增殖、生长和凋亡的关键调节因子,在伯基特淋巴瘤中经常失调。姜科植物——高良姜、黑姜黄、黑姜、白豆蔻和砂仁——传统上用作草药,可能作为天然抗淋巴瘤药物。在本研究中,对这五种植物的提取物进行了针对Raji和Daudi淋巴瘤细胞系的细胞毒性筛选,并将其对淋巴瘤细胞的作用与其对正常外周血单个核细胞(PBMC)的作用进行了比较。高良姜提取物对淋巴瘤细胞表现出最强的细胞毒性作用。其主要生物活性化合物高良姜素和1'-乙酰氧基查维醇乙酸酯(ACA)表现出选择性细胞毒性,其中ACA的作用更强。ACA显著抑制c-Myc和磷酸化c-Myc(p-c-Myc)蛋白水平,并在淋巴瘤细胞中诱导剂量依赖性凋亡。细胞周期分析显示细胞停滞在特定阶段,支持其抗增殖作用。此外,网络药理学和通路富集分析表明ACA参与了致癌性PI3K-Akt和MAPK通路的调节。这些发现突出了ACA作为一种有前景的源自植物的淋巴瘤治疗候选药物,其作用机制是通过抑制c-Myc、使细胞周期停滞和诱导凋亡。