Inhibitory Effect of Arctigenin Derivatives on Tumor Cells and Its Mechanism

LIU Fangfei¹, SHU Hui¹, LIU Dingrui¹, ZHANG Xinhong¹, ZHU Yanbo², ZHAO Yan¹, CAI Enbo¹, HAN Jiahong^1
*

( ¹College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; ² Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Stem Cell and Cancer Center, the First Hospital of Jilin University, Changchun 130021, China)

Abstract:

In this study, a total of 27 ARG (arctigenin) derivatives were designed, of which nine were novel derivatives targeting tumor cell mitochondria. Biological studies showed that all the triphenylphosphine conjugated compounds had a significant increase in anti-tumor activity compared with ARG. Among them, Mito-ARG-7 showed a high selectivity against A549 cells, and its anti-tumor activity was increased by 86.38% compared with ARG. This study showed that the anti-tumor mechanisms of Mito-ARG-7 included significantly increasing the production of reactive oxygen species in A549 cells, causing a decrease in mitochondrial membrane potential, promoting the release of apoptotic protein Cytochrome C from mitochondria to cytoplasm in the endogenous mitochondrial apoptosis signaling pathway, and causing the activation of Caspase family proteins to eventually induce the apoptosis of tumor cells. The novel arctigenin derivative with mitochondrial targeting function synthesized in this study provides a reference for the development of targeted anti-tumor drugs

CSTR: 32200.14.cjcb.2024.06.0011