三阴性乳腺癌
癌症研究
空泡化
体内
程序性细胞死亡
化学
乳腺癌
细胞生长
癌症
体外
细胞凋亡
内科学
医学
生物
生物化学
生物技术
作者
Jia He,Sheng Wang,Dazhao Mi,Tian Guan,Wenjing Liu,Peng He,Haijun Gu,Yuzhan Li,Yangrui Peng,Ai‐Qun Jia,Ceshi Chen,Yihua Chen
标识
DOI:10.1021/acs.jmedchem.3c00090
摘要
Triple-negative breast cancer (TNBC) is a leading malignancy among women that currently lack effective targeted therapeutic agents, and the limitations of treatment have prompted the emergence of new strategies. Methuosis is a novel vacuole-presenting cell death modality that promotes tumor cell death. Hence, a series of pyrimidinediamine derivatives were designed and synthesized through evaluation of their abilities that inhibit proliferation as well as induce methuosis against TNBC cells. Among them, JH530 showed excellent anti-proliferative activities and vacuolization capacity in TNBC. The mechanism research indicated that JH530 caused cell death through inducing methuosis of cancer cells. Furthermore, JH530 inhibited tumor growth remarkably in the HCC1806 xenograft model without an apparent decrease in body weight. Overall, JH530 is a methuosis inducer that displayed remarkable suppression of TNBC growth in vitro and in vivo, which provides a basis for the future progress of more small molecules for TNBC treatment.
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