2. Academic Validation
  3. Microcolin H, a novel autophagy inducer, exerts potent antitumour activity by targeting PITPα/β

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

  • Signal Transduct Target Ther. 2023 Nov 15;8(1):428. doi: 10.1038/s41392-023-01667-2.
Hange Yang # 1,  Xiaowei Zhang # 1,  Cong Wang # 1,  Hailong Zhang # 2,  Juan Yi 1,  Kun Wang 3,  Yanzhe Hou 1,  Peihong Ji 1,  Xiaojie Jin 4,  Chenghao Li 4,  Min Zhang 4,  Shan Huang 1,  Haoyuan Jia 1 5,  Kuan Hu 3,  Lingyun Mou 6 7,  Rui Wang 8 9
Affiliations

Affiliations

  • 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 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. [email protected].
  • 3 Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, P. R. China.
  • 4 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.
  • 5 School of Life Science, Lanzhou University, 730000, Lanzhou, P. R. China.
  • 6 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. [email protected].
  • 7 School of Life Science, Lanzhou University, 730000, Lanzhou, P. R. China. [email protected].
  • 8 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. [email protected].
  • 9 Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, P. R. China. [email protected].
  • # Contributed equally.
PMID: 37963877 DOI: 10.1038/s41392-023-01667-2
Abstract

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/β expression 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/β and 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/β as a promising therapeutic target for Cancer treatment.

Figures
Products