Sophoridine Derivatives Induce Apoptosis and Autophagy to Suppress the Growth of Triple‐Negative Breast Cancer through Inhibition of mTOR Signaling

• DOI: 10.1002/cmdc.202100434
• Publication Date: 2021-09-27T03:08:15Z
• Authors: Linlin Dai; Luyao Wang; Cheng Tan; Jun Cai; Hongsheng Shen; Ting Zhang; Shuang Zhi; Zibo Yang; Yunhui Hu; Xiumei Zhao; Dongdong Li
• Keywords: Triple-negative breast cancer

Abstract In order to improve the antitumor potency and therapeutic margins of natural product sophoridine, its novel nitrogen mustard carbamate derivatives were designed synthesized. screening their in vitro activity, we found all tested compounds more potent against highly aggressive triple‐negative breast cancer cell line MDA‐MB‐231. Cellular functional assays showed that representative could induce G1‐phase arrest trigger apoptosis, evidenced by alteration Bax, Bcl‐2, caspase‐3 PARP levels. Furthermore, these significantly enhanced autophagic flux with increased expression LC3‐II Beclin‐1, as well decreased level p62, which may attribute simultaneously inhibition phosphorylation p70S6K, 4E‐BP1 AKT, key substrates mTOR signaling pathway. vivo, two revealed activity mice bearing Altogether, our work describes leads yield chemotherapeutics cancers, possibly mesenchymal stem‐like subtype.