体内
结直肠癌
细胞凋亡
药理学
细胞毒性
生物碱
自噬
癌症
癌症研究
体外
医学
化学
生物
生物化学
内科学
立体化学
生物技术
作者
Feng Li,Ran-Ran Shang,Xinjia Wang,Ling Li,Xin Li,Yuan-Xiang Gong,Li-Yuan Shi,Jingwen Wang,Yueqing Gu,Ning‐Hua Tan,Zhe Wang
标识
DOI:10.1021/acs.jnatprod.3c00125
摘要
Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (−)-N-hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1–TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo. This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.
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