Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells

  • Authors:
    • Chuan Chen
    • Tongdan Xue
    • Peng Fan
    • Linlin Meng
    • Jingjing Wei
    • Duqiang Luo
  • View Affiliations

  • Published online on: April 27, 2018     https://doi.org/10.3892/ol.2018.8593
  • Pages: 10055-10062
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Abstract

Fumosorinone (Fumos) isolated from entomogenous fungi Isaria fumosorosea exhibited selective inhibition of Src homology phosphotyrosine phosphatase 2 inhibitor (Shp2) in our previous study. The purpose of the present study was to investigate the effects of Fumos on cell cycle arrest, tumor cell migration and the in vitro antiproliferative activity of Fumos alone or in combination with the commonly used cytotoxic drugs 5‑fluoracil (5‑FU) and p38 inhibitor SB203580. Fumos exhibited cytotoxicity against selected human cancel lines, including HeLa, MDA‑MB‑231 and MDA‑MB‑453 cell lines. Fumos exerted selective cytotoxic effects on the human cell lines. Flow cytometric and DAPI assays showed that Fumos did not induce cell apoptosis, however it induced cell cycle arrest at the G1 phase. Fumos inhibited cell migration though reducing the phosphorylation of focal adhesion kinase (FAK) at tyrosine (Tyr)861 and marginally increasing the phosphorylation of FAK at Tyr397, however, Fumos did not affect the phosphorylation of FAK at Tyr576 or Tyr925. The present study also examined the combination effect of Fumos with other chemical agents, including 5‑FU and p38 inhibitor SB203580. Fumos exhibited a marked synergistic effect with these agents, particularly with 5‑FU. In conclusion, Fumos showed potential anticancer bioactivity, and the combination effect of Fumos with 5‑FU or with p38 inhibitor offers a more effective anticancer strategy for carcinoma treatment.
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June-2018
Volume 15 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Chen C, Xue T, Fan P, Meng L, Wei J and Luo D: Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells. Oncol Lett 15: 10055-10062, 2018
APA
Chen, C., Xue, T., Fan, P., Meng, L., Wei, J., & Luo, D. (2018). Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells. Oncology Letters, 15, 10055-10062. https://doi.org/10.3892/ol.2018.8593
MLA
Chen, C., Xue, T., Fan, P., Meng, L., Wei, J., Luo, D."Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells". Oncology Letters 15.6 (2018): 10055-10062.
Chicago
Chen, C., Xue, T., Fan, P., Meng, L., Wei, J., Luo, D."Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells". Oncology Letters 15, no. 6 (2018): 10055-10062. https://doi.org/10.3892/ol.2018.8593