Arsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and enhance the sensitivity of myeloma cells to Bortezomib.

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Zhou L, Hou J, Fu W, Wang D, Yuan Z, Jiang H

Arsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and enhance the sensitivity of myeloma cells to Bortezomib.

Leuk Res. 2008 Nov;32(11):1674-83. doi: 10.1016/j.leukres.2008.03.039. Epub 2008 May 15.

PubMed ID

18485479 [ View in PubMed

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Abstract

Beta-catenin, the key protein in canonical Wingless/int (Wnt) pathway, degrades via ubiquitin-proteasome pathway. Recently, it proved important roles in the proliferation of myeloma cells. But little is known about whether cytoplasmic beta-catenin content is associated with myeloma cell's sensitivity to Bortezomib. We examined the constitutive expression of beta-catenin in five myeloma cell lines and primary cells from patients. Meanwhile, the effect of Bortezomib combined with arsenic trioxide (As(2)O(3))/2-methoxyestradiol (2ME2) on beta-catenin accumulation, myeloma cells' survival, apoptosis and their sensitivity to Bortezomib were also investigated. Our study proved that beta-catenin protein levels are negatively associated with myeloma cells' sensitivity to Bortezomib. As(2)O(3)/2ME2 can reduce cytoplasmic beta-catenin accumulation after proteasome inhibition and enhance myeloma cells' sensitivity to Bortezomib. This will preliminarily help to optimize the new therapeutic regimens for MM treatment in the future.

DrugBank Data that Cites this Article

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
2-Methoxyestradiol	Investigational	CTNNB1	1499	downregulated	2-methoxyestradiol results in decreased expression of CTNNB1 mRNA	3p22.1
Arsenic trioxide	Approved Investigational	CTNNB1	1499	downregulated	arsenic trioxide results in decreased expression of CTNNB1 mRNA	3p22.1