Microcolin H, a novel autophagy inducer, exerts potent antitumour activity by targeting PITPα/β  

作　　者：Hange Yang Xiaowei Zhang Cong Wang Hailong Zhang Juan Yi Kun Wang Yanzhe Hou Peihong Ji Xiaojie Jin Chenghao Li Min Zhang Shan Huang Haoyuan Jia Kuan Hu Lingyun Mou Rui Wang 

机构地区：[1]Key Laboratory of Preclinical Study for New Drugs of Gansu Province,School of Basic Medical Sciences&Research Unit of Peptide Science,Chinese Academy of Medical Sciences,2019RU066,Lanzhou University,Lanzhou,Gansu,P.R.China [2]Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing,P.R.China [3]Gansu University Key Laboratory for Molecular Medicine&Chinese Medicine Prevention and Treatment of Major Diseases,College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou,China [4]School of Life Science,Lanzhou University,730000 Lanzhou,P.R.China

出　　处：《Signal Transduction and Targeted Therapy》2023年第12期5931-5943,共13页信号转导与靶向治疗（英文）

基　　金：supported by the Program for the Ministry of Education“Peptide Drugs”Innovation Team(No.IRT_15R27,China);the National Natural Science Foundation of China(21807053);the CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2019-I2M-5-074,2021-I2M-1-026,2021-I2M-3-001,2022-I2M-2-002,China);the Fundamental Research Funds for the Central Universities(No.lzujbky-2023-11,lzujbky-2023-ct02,lzujbky-2023-it19,China).

摘　　要：The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy.The phosphatidylinositol transfer protein alpha/beta isoform(PITPα/β)has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment.Herein,data analysis of clinical cancer samples revealed that PITPα/βexpression is closely correlated with the poor prognosis.Target identification by chemical proteomic methods revealed that microcolin H,a naturally occurring marine lipopeptide,directly binds PITPα/βand displays antiproliferative activity on different types of tumour cell lines.Furthermore,we identified that microcolin H treatment increased the conversion of LC3I to LC3II,accompanied by a reduction of the level of p62 in cancer cells,leading to autophagic cell death.Moreover,microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity.Our discoveries revealed that by targeting PITPα/β,microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity,which sheds light on PITPα/βas a promising therapeutic target for cancer treatment.

关 键 词：TUMOUR METABOLISM NUDE 

分 类 号：R730.5[医药卫生—肿瘤]