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Alpha-mangostin reduces mechanical stiffness of various cells

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Abstract

Alpha-mangostin (α-mangostin) has been identified as a naturally occurring compound with potential anticancer properties. It can induce apoptosis and inhibit the growth and metastasis of cancer cells. Moreover, α-mangostin reduces the mechanical stiffness of lung cancer cells. The objective of this study was to determine the effect of α-mangostin on the mechanical stiffness of various cells, as well as cell viability. The following cell types were examined: human fibroblast TIG-1 cells, human cancerous HeLa cells, human embryonic kidney HEK293 cells, mouse macrophage RAW 264.7 cells, and human myeloblasts KG-1 cells. Cells were treated with α-mangostin, and then examined for cell viability, actin cytoskeletal structures, and surface mechanical stiffness using atomic force microscopy. α-Mangostin demonstrated cytotoxicity against TIG-1, HeLa, HEK293, and KG-1 cells, but not against RAW 264.7 cells. The cytotoxic effect of α-mangostin varies according to cell type. On the other hand, α-mangostin reduced the mechanical stiffness of all cell types, including RAW 264.7 cells. Upon treatment with α-mangostin, F-actin was slightly reduced but the actin cytoskeletal structures were little altered in these cells. Thus, reducing mechanical stiffness of animal cells is an inherent effect of α-mangostin. Our results show that α-mangostin is a naturally occurring compound with potential to change the actin cytoskeletal micro-structures and reduce the surface stiffness of various cells.

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References

  1. Chen G, Li Y, Wang W, Deng L. Bioactivity and pharmacological properties of alpha-mangostin from the mangosteen fruit: a review. Expert Opin Ther Pat. 2018;28(5):415–27.

    CAS  PubMed  Google Scholar 

  2. Watanapokasin R, Jarinthanan F, Nakamura Y, Sawasjirakij N, Jaratrungtawee A, Suksamrarn S. Effects of alpha-mangostin on apoptosis induction of human colon cancer. World J Gastroenterol. 2011;17(16):2086–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Kaomongkolgit R, Chaisomboon N, Pavasant P. Apoptotic effect of alpha-mangostin on head and neck squamous carcinoma cells. Arch Oral Biol. 2011;56(5):483–90.

    CAS  PubMed  Google Scholar 

  4. Lee CH, Ying TH, Chiou HL, Hsieh SC, Wen SH, Chou RH, et al. Alpha-mangostin induces apoptosis through activation of reactive oxygen species and ASK1/p38 signaling pathway in cervical cancer cells. Oncotarget. 2017;8(29):47425–39.

    PubMed  PubMed Central  Google Scholar 

  5. Hung SH, Shen KH, Wu CH, Liu CL, Shih YW. Alpha-mangostin suppresses PC-3 human prostate carcinoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen expression through the JNK signaling pathway. J Agric Food Chem. 2009;57(4):1291–8.

    CAS  PubMed  Google Scholar 

  6. Lee YB, Ko KC, Shi MD, Liao YC, Chiang TA, Wu PF, et al. alpha-Mangostin, a novel dietary xanthone, suppresses TPA-mediated MMP-2 and MMP-9 expressions through the ERK signaling pathway in MCF-7 human breast adenocarcinoma cells. J Food Sci. 2010;75(1):H13–23.

    CAS  PubMed  Google Scholar 

  7. Shih YW, Chien ST, Chen PS, Lee JH, Wu SH, Yin LT. Alpha-mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via alphavbeta3 integrin/FAK/ERK and NF-kappaB signaling pathway in human lung adenocarcinoma A549 cells. Cell Biochem Biophys. 2010;58(1):31–44.

    CAS  PubMed  Google Scholar 

  8. Pedraza-Chaverri J, Reyes-Fermin LM, Nolasco-Amaya EG, Orozco-Ibarra M, Medina-Campos ON, Gonzalez-Cuahutencos O, et al. ROS scavenging capacity and neuroprotective effect of alpha-mangostin against 3-nitropropionic acid in cerebellar granule neurons. Exp Toxicol Pathol. 2009;61(5):491–501.

    CAS  PubMed  Google Scholar 

  9. Phan TKT, Shahbazzadeh F, Pham TTH, Kihara T. Alpha-mangostin inhibits the migration and invasion of A549 lung cancer cells. PeerJ. 2018;6:e5027.

    PubMed  PubMed Central  Google Scholar 

  10. Dai J, Sheetz MP. Mechanical properties of neuronal growth cone membranes studied by tether formation with laser optical tweezers. Biophys J. 1995;68(3):988–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Collinsworth AM, Zhang S, Kraus WE, Truskey GA. Apparent elastic modulus and hysteresis of skeletal muscle cells throughout differentiation. Am J Physiol Cell Physiol. 2002;283(4):C1219–C12271227.

    CAS  PubMed  Google Scholar 

  12. Guilak F, Erickson GR, Ting-Beall HP. The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes. Biophys J. 2002;82(2):720–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Trickey WR, Vail TP, Guilak F. The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. J Orthop Res. 2004;22(1):131–9.

    PubMed  Google Scholar 

  14. Haghparast SM, Kihara T, Shimizu Y, Yuba S, Miyake J. Actin-based biomechanical features of suspended normal and cancer cells. J Biosci Bioeng. 2013;116(3):380–5.

    CAS  PubMed  Google Scholar 

  15. Haghparast SM, Kihara T, Miyake J. Distinct mechanical behavior of HEK293 cells in adherent and suspended states. PeerJ. 2015;3:e1131.

    PubMed  PubMed Central  Google Scholar 

  16. Matzke R, Jacobson K, Radmacher M. Direct, high-resolution measurement of furrow stiffening during division of adherent cells. Nat Cell Biol. 2001;3(6):607–10.

    CAS  PubMed  Google Scholar 

  17. Kunda P, Pelling AE, Liu T, Baum B. Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis. Curr Biol. 2008;18(2):91–101.

    CAS  PubMed  Google Scholar 

  18. Fletcher DA, Mullins RD. Cell mechanics and the cytoskeleton. Nature. 2010;463(7280):485–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Shimizu Y, Haghparast SM, Kihara T, Miyake J. Cortical rigidity of round cells in mitotic phase and suspended state. Micron. 2012;43(12):1246–51.

    CAS  PubMed  Google Scholar 

  20. Radmacher M, Fritz M, Kacher CM, Cleveland JP, Hansma PK. Measuring the viscoelastic properties of human platelets with the atomic force microscope. Biophys J. 1996;70(1):556–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Rotsch C, Braet F, Wisse E, Radmacher M. AFM imaging and elasticity measurements on living rat liver macrophages. Cell Biol Int. 1997;21(11):685–96.

    CAS  PubMed  Google Scholar 

  22. Haga H, Sasaki S, Kawabata K, Ito E, Ushiki T, Sambongi T. Elasticity mapping of living fibroblasts by AFM and immunofluorescence observation of the cytoskeleton. Ultramicroscopy. 2000;82(1–4):253–8.

    CAS  PubMed  Google Scholar 

  23. Kihara T, Haghparast SM, Shimizu Y, Yuba S, Miyake J. Physical properties of mesenchymal stem cells are coordinated by the perinuclear actin cap. Biochem Biophys Res Commun. 2011;409(1):1–6.

    CAS  PubMed  Google Scholar 

  24. Kagiwada H, Nakamura C, Kihara T, Kamiishi H, Kawano K, Nakamura N, et al. The mechanical properties of a cell, as determined by its actin cytoskeleton, are important for nanoneedle insertion into a living cell. Cytoskeleton (Hoboken). 2010;67(8):496–503.

    CAS  Google Scholar 

  25. Shimizu Y, Kihara T, Haghparast SM, Yuba S, Miyake J. Simple display system of mechanical properties of cells and their dispersion. PLoS ONE. 2012;7(3):e34305.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Cross SE, Jin YS, Lu QY, Rao J, Gimzewski JK. Green tea extract selectively targets nanomechanics of live metastatic cancer cells. Nanotechnology. 2011;22(21):215101.

    PubMed  PubMed Central  Google Scholar 

  27. Ramos JR, Pabijan J, Garcia R, Lekka M. The softening of human bladder cancer cells happens at an early stage of the malignancy process. Beilstein J Nanotechnol. 2014;5:447–57.

    PubMed  PubMed Central  Google Scholar 

  28. Kihara T, Nakamura C, Suzuki M, Han S-W, Fukazawa K, Ishihara K, et al. Development of a method to evaluate caspase-3 activity in a single cell using a nanoneedle and a fluorescent probe. Biosens Bioelectron. 2009;25(1):22–7.

    CAS  PubMed  Google Scholar 

  29. Kim KS, Cho CH, Park EK, Jung MH, Yoon KS, Park HK. AFM-detected apoptotic changes in morphology and biophysical property caused by paclitaxel in Ishikawa and HeLa cells. PLoS ONE. 2012;7(1):e30066.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kato K, Umezawa K, Funeriu DP, Miyake M, Miyake J, Nagamune T. Immobilized culture of nonadherent cells on an oleyl poly(ethylene glycol) ether-modified surface. Biotechniques. 2003;35(5):1014–21.

    CAS  PubMed  Google Scholar 

  31. Hertz H. Über die berührung fester elastischer Körper. J Reine Angewandte Math. 1881;92:156–71.

    Google Scholar 

  32. Chen LG, Yang LL, Wang CC. Anti-inflammatory activity of mangostins from Garcinia mangostana. Food Chem Toxicol. 2008;46(2):688–93.

    CAS  PubMed  Google Scholar 

  33. Ohnishi H, Sasaki H, Nakamura Y, Kato S, Ando K, Narimatsu H, et al. Regulation of cell shape and adhesion by CD34. Cell Adh Migr. 2013;7(5):426–33.

    PubMed  PubMed Central  Google Scholar 

  34. Tachibana K, Ohnishi H, Ali Haghparast SM, Kihara T, Miyake J. Activation of PKC induces leukocyte adhesion by the dephosphorylation of ERM. Biochem Biophys Res Commun. 2020;523(1):177–82.

    PubMed  Google Scholar 

  35. von Andrian UH, Hasslen SR, Nelson RD, Erlandsen SL, Butcher EC. A central role for microvillous receptor presentation in leukocyte adhesion under flow. Cell. 1995;82(6):989–99.

    Google Scholar 

  36. Majstoravich S, Zhang J, Nicholson-Dykstra S, Linder S, Friedrich W, Siminovitch KA, et al. Lymphocyte microvilli are dynamic, actin-dependent structures that do not require Wiskott-Aldrich syndrome protein (WASp) for their morphology. Blood. 2004;104(5):1396–403.

    CAS  PubMed  Google Scholar 

  37. Yamane J, Ohnishi H, Sasaki H, Narimatsu H, Ohgushi H, Tachibana K. Formation of microvilli and phosphorylation of ERM family proteins by CD43, a potent inhibitor for cell adhesion: cell detachment is a potential cue for ERM phosphorylation and organization of cell morphology. Cell Adh Migr. 2011;5(2):119–32.

    PubMed  PubMed Central  Google Scholar 

  38. Jinsart W, Ternai B, Buddhasukh D, Polya GM. Inhibition of wheat embryo calcium-dependent protein kinase and other kinases by mangostin and gamma-mangostin. Phytochemistry. 1992;31(11):3711–3.

    CAS  PubMed  Google Scholar 

  39. Liu Y, Park JM, Chang KH, Chin YW, Lee MY. alpha- and gamma-mangostin cause shape changes, inhibit aggregation and induce cytolysis of rat platelets. Chem Biol Interact. 2015;240:240–8.

    CAS  PubMed  Google Scholar 

  40. Furukawa K, Shibusawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y. The mode of inhibitory action of alpha-mangostin, a novel inhibitor, on the sarcoplasmic reticulum Ca(2+)-pumping ATPase from rabbit skeletal muscle. Jpn J Pharmacol. 1996;71(4):337–40.

    CAS  PubMed  Google Scholar 

  41. Itoh T, Ohguchi K, Iinuma M, Nozawa Y, Akao Y. Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation. Bioorg Med Chem. 2008;16(8):4500–8.

    CAS  PubMed  Google Scholar 

  42. Tao M, Jiang J, Wang L, Li Y, Mao Q, Dong J, et al. alpha-mangostin alleviated lipopolysaccharide induced acute lung injury in rats by suppressing NAMPT/NAD controlled inflammatory reactions. Evid Based Complement Alternat Med. 2018;2018:5470187.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by JSPS KAKENHI Grant no. 16K01368 to T.K. and grant for Young Scientists, Institute of Environmental Science and Technology, The University of Kitakyushu to T.K.

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  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, Fahimeh Shahbazzadeh & Takanori Kihara

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  1. Thi Kieu Trang Phan
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  2. Fahimeh Shahbazzadeh
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Correspondence to Takanori Kihara.

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Phan, T.K.T., Shahbazzadeh, F. & Kihara, T. Alpha-mangostin reduces mechanical stiffness of various cells. Human Cell 33, 347–355 (2020). https://doi.org/10.1007/s13577-020-00330-0

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