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Quinovic Acid 通过调节 Ras/MAPK 信号通路和干扰素-γ 表达增强 KHYG-1 细胞的细胞毒性

英文原题:Quinovic Acid Enhances the Cytotoxicity of KHYG-1 Cells by Modulating the Ras/MAPK Signalling Pathway and Interferon-Gamma Expression.

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Quinovic Acid Enhances the Cytotoxicity of KHYG-1 Cells by Modulating the Ras/MAPK Signalling Pathway and Interferon-Gamma Expression.

PubMed 2025/11/01(内容时间) J Cell Mol Med Q2 · IF 4.7(JCR 2025)

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中文摘要

喹诺酸是猫爪草(Uncaria tomentosa)提取物的关键成分,具有抗氧化和抗炎活性。在本研究中,我们利用KHYG-1细胞系探讨了喹诺酸增强自然杀伤(NK)细胞活性的潜力。

我们的数据表明,喹诺酸增加了溶细胞分子的表达水平,包括穿孔素、颗粒酶A和B、Fas配体以及颗粒溶素,并诱导转录因子CREB和STAT4的磷酸化,从而增强了对K562细胞的细胞毒活性。

此外,当KHYG-1细胞在喹诺酸存在下与K562细胞共培养时,我们观察到t-Bid、cleaved caspases 3、8和9以及PARP的表达增加,促进了K562细胞的凋亡。喹诺酸还降低了SET、Ape1和HMGB2的表达,有效抑制了靶细胞中的DNA修复机制。在其他癌细胞系中也观察到了类似的结果。

此外,喹诺酸通过激活NKG2D和其他NK受体,上调Ras/MAPK和PI3K/AKT/mTOR信号通路,从而诱导干扰素-γ的分泌。这些效应不仅在KHYG-1细胞中观察到,也在来自成人头颈部鳞状细胞癌患者的NK细胞中观察到。

我们的研究结果表明,喹诺酸增强NK细胞细胞毒性,显示出作为针对多种癌细胞类型的潜在治疗药物的前景。

展开英文摘要原文

Quinovic acid is a key constituent of cat's claw (Uncaria tomentosa) extract and exhibits antioxidant and anti-inflammatory activities. In this study, we investigated the potential of quinovic acid to enhance natural killer (NK) cell activity by using the KHYG-1 cell line.

Our data indicated that quinovic acid increased the expression levels of cytolytic molecules, including perforin, granzymes A and B, Fas ligand, and granulysin, and induced the phosphorylation of the transcription factors CREB and STAT4, thereby enhancing cytotoxic activity against K562 cells.

Furthermore, when KHYG-1 cells were cocultured with K562 cells in the presence of quinovic acid, we observed an increase in the expression of t-Bid, cleaved caspases 3, 8, and 9, and PARP, promoting apoptosis in K562 cells. Quinovic acid also reduced the expression of SET, Ape1, and HMGB2, effectively inhibiting the DNA repair mechanism in target cells. Similar results were observed in other cancer cell lines.

In addition, quinovic acid induced interferon-gamma secretion by upregulating the Ras/MAPK and PI3K/AKT/mTOR signalling pathways through the activation of NKG2D and other NK receptors. These effects were observed not only in KHYG-1 cells but also in NK cells derived from adult patients with head and neck squamous cell carcinoma.

Our findings suggest that quinovic acid enhances NK cell cytotoxicity, showing promise as a potential therapeutic against various cancer cell types.

论文信息

作者
Hsieh MJ、Lin JT、Chuang YC、Ho HY、Lo YS、Lin CC、Chen MK
第一作者单位
Oral Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.Taiwan
通讯作者单位
Graduate Institute of Clinical Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.Taiwan
文献类型
非美国政府资助研究
期刊
Journal of cellular and molecular medicine2025 Nov
原文标识
PubMed 41294043 · DOI 10.1111/jcmm.70957