Curcumin Analog L48H37 Induces Apoptosis in Human Oral Cancer Cells by Activating Caspase Cascades and Downregulating the Inhibitor of Apoptosis Proteins through JNK/p38 Signaling.

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-03-14 DOI:10.1142/S0192415X24500241
Chun-Wen Su, Shao-Hsuan Kao, Yi-Tzu Chen, Yi-Hsien Hsieh, Wei-En Yang, Meng-Ying Tsai, Chiao-Wen Lin, Shun-Fa Yang
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Abstract

L48H37 is a synthetic curcumin analog that has anticancer potentials. Here, we further explored the anticancer effect of L48H37 on oral cancer cells and its mechanistic acts. Cell cycle distribution was assessed using flow cytometric analysis. Apoptosis was elucidated by staining with PI/Annexin V and activation of the caspase cascade. Cellular signaling was explored using apoptotic protein profiling, Western blotting, and specific inhibitors. Our findings showed that L48H37 significantly reduced the cell viability of SCC-9 and HSC-3 cells, resulting in sub-G1 phase accumulation and increased apoptotic cells. Apoptotic protein profiling revealed that L48H37 increased cleaved caspase-3, and downregulated cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) in SCC-9 cells, and the downregulated cIAP1 and XIAP in both oral cancer cells were also demonstrated by Western blotting. Meanwhile, L48H37 triggered the activation of caspases and mitogen-activated protein kinases (MAPKs). The involvement of c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) in the L48H37-triggered apoptotic cascade in oral cancer cells was also elucidated by specific inhibitors. Collectively, these findings indicate that L48H37 has potent anticancer activity against oral cancer cells, which may be attributed to JNK/p38-mediated caspase activation and the resulting apoptosis. This suggests a potential benefit for L48H37 for the treatment of oral cancer.

姜黄素类似物 L48H37 通过 JNK/p38 信号激活 Caspase 级联和下调凋亡抑制蛋白诱导人口腔癌细胞凋亡
L48H37 是一种具有抗癌潜力的合成姜黄素类似物。在此,我们进一步探讨了 L48H37 对口腔癌细胞的抗癌作用及其机理作用。细胞周期分布采用流式细胞分析法进行评估。通过 PI/Annexin V 染色和 caspase cascade 激活来阐明细胞凋亡。利用凋亡蛋白图谱、Western 印迹和特异性抑制剂探索了细胞信号传导。我们的研究结果表明,L48H37 能显著降低 SCC-9 和 HSC-3 细胞的存活率,导致亚 G1 期积累和凋亡细胞增加。凋亡蛋白图谱显示,L48H37增加了SCC-9细胞中裂解的caspase-3,下调了细胞凋亡抑制蛋白1(cIAP1)和X-连锁凋亡抑制蛋白(XIAP)。同时,L48H37 引发了 Caspases 和丝裂原活化蛋白激酶(MAPKs)的活化。特异性抑制剂也阐明了 c-Jun N 端激酶(JNK)和 p38 MAPK(p38)参与 L48H37 触发的口腔癌细胞凋亡级联反应。总之,这些研究结果表明,L48H37 对口腔癌细胞具有很强的抗癌活性,这可能归因于 JNK/p38 介导的 caspase 激活和由此产生的细胞凋亡。这表明 L48H37 有助于治疗口腔癌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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