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BMI1 Inhibitors Down-regulate NOTCH Signaling and Suppress Proliferation of Acute Leukemia Cells

BMI1 Inhibitors Down-regulate NOTCH Signaling and Suppress Proliferation of Acute Leukemia Cells

Mika Ohtaka, Mai Itoh, Shuji Tohda

Anticancer Res. 2017 Nov;37(11):6047-6053.

PMID: 29061784

Abstract:

Background/aim:
B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells.
Materials and methods:
Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting.
Results:
PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis.Artemisinin acted only on Jurkat cells. BMI1 inhibitors and BMI1-specific siRNA down-regulated the expression of NOTCH signaling proteins NOTCH1, HES1, and MYC. All but one cell lines did not have the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene targeted by BMI1, thus the inhibitors acted through CDKN2A-independent pathways.
Conclusion:
BMI1 inhibition suppressed proliferation of leukemia cells through NOTCH signaling which functions downstream of BMI1, suggesting that BMI1 inhibitors can be candidate targeted drugs against leukemia.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP31083553	PRT4165		31083-55-3	Price

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