2. Academic Validation
  3. Cytotoxic effects of recombinant proteins enhanced by momordin Ic are dependent on cholesterol and ganglioside GM1

Cytotoxic effects of recombinant proteins enhanced by momordin Ic are dependent on cholesterol and ganglioside GM1

  • Toxicon. 2023 Jun 15:229:107129. doi: 10.1016/j.toxicon.2023.107129.
Wei Wang 1,  Xue-Wei Cao 2,  Fu-Jun Wang 3,  Jian Zhao 4
Affiliations

Affiliations

  • 1 Department of Applied Biology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  • 2 Department of Applied Biology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China; ECUST-FONOW Joint Research Center for Innovative Medicines, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  • 3 ECUST-FONOW Joint Research Center for Innovative Medicines, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China; New Drug R&D Center, Zhejiang Fonow Medicine Co., Ltd. 209 West Hulian Road, Dongyang, 322100, Zhejiang, China; Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. Electronic address: wfj@shutcm.edu.cn.
  • 4 Department of Applied Biology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China; ECUST-FONOW Joint Research Center for Innovative Medicines, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. Electronic address: zhaojian@ecust.edu.cn.
PMID: 37086901 DOI: 10.1016/j.toxicon.2023.107129
Abstract

Plant-derived triterpenoid saponins have been shown to play a powerful role in enhancing the cytotoxic activity of protein therapeutics. However, the mechanism of how saponins are acting is not clearly understood. In this study, momordin Ic (MIC), a triterpenoid saponin derived from Kochia scoparia (L.) Schrad., specifically enhance the antiproliferative effect of recombinant MAP30 (a type I ribosome inactivating protein, RIP) in breast Cancer cells. Subsequently, the possible mechanism of how MIC enhanced the cytotoxicity of MAP30 was analyzed in detail. We observed the level of intracellular labeled MAP30 using fluorescence microscopy and flow cytometry. And a reporter protein, GAL9, was used to monitor the role of MIC in promoting endosomal escape. We found endosomal escape does not play a role for the enhancer effect of MIC while the effect of MIC on MAP30 is Cholesterol dependent and that ganglioside GM1, a lipid raft marker, can competitively inhibit cytotoxicity of MAP30 enhanced by MIC. Finally, we provided some insights into the correlation between the sugar side chain of MIC and its role in enhancing of RIP cytotoxicity and altering of drug cell tropism.

Keywords

Cell specificity; Ganglioside GM1; Momordin Ic; Ribosome inactivating protein (RIP); Triple-negative breast cancer cells.

Figures
Products