8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells

8-甲氧基弗林德辛诱导人类结肠直肠癌细胞凋亡和细胞周期紊乱,涉及 MAPK 信号激活

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作者:Dianbao Zhang, Yunmei Fu, Ying Liu, Yifan Wu, Jiayu Chen, Luting Zhang, Rui Wang, Zaixing Chen, Tao Liu

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors with a high lethal rate globally, and novel strategies for its prevention and therapy are urgently needed. In our previous work, 8-methoxyflindersine (8-MF), a quinoline alkaloid, was isolated from the Dictamni cortex, and its bioactivities were largely unknown. In this study, we found that 8-MF significantly inhibited cell viability in the CRC cell lines LoVo and RKO. The 8-MF-induced CRC cell apoptosis, as well as cell cycle disorder, were further verified by cyclins dysregulation in mRNA and protein levels. Further, the activation of MAPK family members p38 and ERK1/2 was observed after 8-MF treatment. Moreover, the protein-protein interaction of 8-MF with cyclins and MAPKs was demonstrated using the STRING database. The 8-MF could bind to p38 and ERK1/2 proteins in molecular docking. Taken together, we found that 8-MF induced apoptosis and cell cycle disorder involving MAPK signaling activation in CRC cells, indicating 8-MF as a novel lead compound candidate for the development of anti-tumor drugs for CRC.

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