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INNO-406 inhibits the growth of chronic myeloid leukemia and promotes its apoptosis via targeting PTEN

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Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. INNO-406 is a novel tyrosine kinase inhibitor (TKI) that possess specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. The present study aimed to confirm the anti-tumor effect of INNO-406 on CML cells, and elucidate the underlying molecular mechanism. CML cells were treated by INNO-406 at the concentration of 5, 25, 50, 100 μM at the indicated time. Cell proliferation was measured by MTT. Cell apoptosis were detected by Western blot and flow cytometry, respectively. As suggested by the findings, INNO-406 significantly inhibited the proliferation and induced apoptosis of CML cells. In addition, INNO-406 promoted the expression level of PTEN. Rescue experiment revealed that PTEN knockdown reversed the effect of INNO-406 which indicated the correlation between INNO-406 and PTEN. Further study determined that PTEN inhibited the phosphorylation of AKT and 4EBP1 and subsequently altered the expression of apoptotic proteins including bax, cytoplasmic cytochrome c (cyto-c), cleaved caspase3 and bcl-2. In vivo study further confirmed that INNO-406 inhibited the growth of CML cells by targeting PTEN. Based on the above findings, this work extended our understanding of INNO-406 in the therapy of CML and its molecular mechanism.

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Data accessibility

All data is available at the request of corresponding author.

Abbreviations

CML:

Chronic myeloid leukemia

ABL:

Abelson murine leukemia

BCR:

Breakpoint cluster region

TKIs:

Tyrosine kinase inhibitors

BCA:

Bicinchoninic acid assay

SDS-PAGE:

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis

ECL:

Enhanced chemiluminescence

OD:

Optical densities

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Authors and Affiliations

  1. Department of Pediatric Hematology, Affiliated Hospital of Qingdao University, Huangdao District, 1677 Wutaishan Road, Qingdao, 266555, Shandong, China

    Jiandong Sun, Yilin Wang & Lirong Sun

Authors
  1. Jiandong Sun
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  2. Yilin Wang
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  3. Lirong Sun
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Contributions

SUN J acquired the data, WANG Y helped analysis data, SUN L supervised the project.

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Correspondence to Lirong Sun.

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Sun, J., Wang, Y. & Sun, L. INNO-406 inhibits the growth of chronic myeloid leukemia and promotes its apoptosis via targeting PTEN. Human Cell 33, 1112–1119 (2020). https://doi.org/10.1007/s13577-020-00413-y

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  • DOI: https://doi.org/10.1007/s13577-020-00413-y

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