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Alpha-mangostin dephosphorylates ERM to induce adhesion and decrease surface stiffness in KG-1 cells

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Abstract

Surface stiffness is a unique indicator of various cellular states and events and needs to be tightly controlled. α-Mangostin, a natural compound with numerous bioactivities, reduces the mechanical stiffness of various cells; however, the mechanism by which it affects the actin cytoskeleton remains unclear. We aimed to elucidate the mechanism underlying α-mangostin activity on the surface stiffness of leukocytes. We treated spherical non-adherent myelomonocytic KG-1 cells with α-mangostin; it clearly reduced their surface stiffness and disrupted their microvilli. The α-mangostin-induced reduction in surface stiffness was inhibited by calyculin A, a protein phosphatase inhibitor. α-Mangostin also induced KG-1 cell adhesion to a fibronectin-coated surface. In KG-1 cells, a decrease in surface stiffness and the induction of cell adhesion are largely attributed to the dephosphorylation of ezrin/radixin/moesin proteins (ERMs); α-mangostin reduced the levels of phosphorylated ERMs. It further increased protein kinase C (PKC) activity. α-Mangostin-induced KG-1 cell adhesion and cell surface softness were inhibited by the PKC inhibitor GF109203X. The results of the present study suggest that α-mangostin decreases stiffness and induces adhesion of KG-1 cells via PKC activation and ERM dephosphorylation.

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Acknowledgements

This work was partly conducted at the Instrumentation Center, The University of Kitakyushu.

Funding

This work was supported by JSPS KAKENHI Grant Number JP21K04797, MEXT Promotion of Distinctive Joint Research Center Program Grant Number JPMXP0621467946, and grant for Young Scientists, Institute of Environmental Science and Technology, The University of Kitakyushu.

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Author notes

  1. Thi Kieu Trang Phan and Thi Ly Do contributed equally.

Authors and Affiliations

  1. Department of Life and Environment Engineering, Faculty of Environmental Engineering, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu, Kitakyushu, Fukuoka, 808-0135, Japan

    Thi Kieu Trang Phan, Thi Ly Do & Takanori Kihara

  2. Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Health Care System, 458 Minh Khai, Hai Ba Trung, Hanoi, Vietnam

    Thi Kieu Trang Phan

  3. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Kouichi Tachibana

  4. Department of Hematology and Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Kouichi Tachibana

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  1. Thi Kieu Trang Phan
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Contributions

TKTP, KT, and TK conceived and designed the work. TKTP, TLD, and TK performed the experiments. TKTP, TLD, KT, and TK analyzed and interpreted the data. TKTP, TLD, and TK drafted the manuscript. KT revised the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Takanori Kihara.

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This work does not involve human participants or their data. In this study, we used KG-1 cell line RRID:CVCL_0374 and U937 DE-4 cell line RRID:CVCL_8765, which obtained from RIKEN BioResource Center (Ibaraki, Japan).

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Phan, T.K.T., Do, T.L., Tachibana, K. et al. Alpha-mangostin dephosphorylates ERM to induce adhesion and decrease surface stiffness in KG-1 cells. Human Cell 35, 189–198 (2022). https://doi.org/10.1007/s13577-021-00651-8

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