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Anticancer research

Anticancer research

IF: 1.6
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Effects of YAP Inhibitors and Activators on the Growth of Leukemia Cells

Published:1 March 2025 DOI: 10.21873/anticanres.17485 PMID: 40037875
Honoka Sezutsu,?Mai Itoh,?Shuji Tohda

Abstract

Background/aim: The Hippo signaling pathway is involved in cell proliferation through the regulation of its downstream molecule YAP. The dysregulation of Hippo signaling is associated with cancer cell proliferation. This study aimed to investigate the effects of YAP inhibitors and activators on the proliferation of human leukemia cell lines in vitro to examine whether YAP functions as a tumor suppressor or promoter.

Materials and methods: In total, six leukemia cell lines (THP-1, HL-60, and U-937, derived from acute myeloid leukemia; K-562 from chronic myeloid leukemia; and KOPT-K1 and Jurkat from T-lymphoblastic leukemia) were treated with the YAP inhibitors CA3, Peptide17, and Verteporfin or YAP activators SBP-3264 and XMU-MP-1. Colorimetric assay was conducted to assess cell growth. Immunoblotting was used to evaluate the expression of signaling proteins.

Results: Treatment with YAP activators suppressed cell growth in all cell lines, with apoptotic induction involving an increase in cleaved caspase-3. Moreover, the treatment down-regulated NOTCH1, cleaved NOTCH1, and MYC expression. Treatment with the YAP inhibitor CA3 suppressed the growth of HL-60 and KOPT-K1 cells without inducing apoptosis, accompanied by decreased MYC expression. As the other two YAP inhibitors did not suppress growth, off-target effects might contribute to inhibition by CA3.

Conclusion: YAP activators suppressed the growth of leukemia cells through induction of apoptosis. This suggested that YAP might function as a tumor suppressor in leukemia. SBP-3264 and XMU-MP-1 could be novel candidate molecular-targeted drugs for leukemia; however, further investigations are required.

Substances (18)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Verteporfin 129497-78-5 2C41H42N4O8 249 suppliers $24.00-$4655.00
Verteporfin 129497-78-5 2C41H42N4O8 249 suppliers $24.00-$4655.00
Verteporfin 129497-78-5 2C41H42N4O8 249 suppliers $24.00-$4655.00
Verteporfin 129497-78-5 2C41H42N4O8 249 suppliers $24.00-$4655.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 113 suppliers $17.00-$4741.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 113 suppliers $17.00-$4741.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 113 suppliers $17.00-$4741.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 113 suppliers $17.00-$4741.00
CIL56 300802-28-2 C23H27N3O5S2 92 suppliers $16.00-$3772.00
CIL56 300802-28-2 C23H27N3O5S2 92 suppliers $16.00-$3772.00

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