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Functional inhibition of BCL2 is needed to increase the susceptibility to apoptosis to SMO inhibitors in diffuse large B-cell lymphoma of germinal center subtype.
MedLine Citation:
PMID:  23370596     Owner:  NLM     Status:  Publisher    
Previously, we have demonstrated that inhibition of Hedgehog pathway induces predominantly apoptosis in diffuse large B-cell lymphoma (DLBCL) cell lines of activated B-cell (ABC) type but predominantly cell cycle arrest in those of germinal center (GC). Here, we explored the possibility of overcoming the resistance to apoptosis to SMO inhibitors in five DLBCL cells of GC type using the combination of the SMO inhibitor HhAntag (Genentech Inc) with the BH3 mimetic ABT-737 (Abbott Laboratories). As controls we have used two DLBCL of ABC type (OCI-LY10 and OCI-LY3). Combinatorial treatments were performed with increasing concentrations of the HhAntag with low doses (equal or less than the IC(20)) of ABT-737. MTS assays were used to detect changes in cell viability and Annexin-V and PARP1 cleavage assays were used to detect apoptosis. Combining low doses of ABT-737 with increasing concentrations of HhAntag in GC DLBCL cell lines resulted in significantly increase of apoptosis in comparison to treatments with the SMO inhibitor alone. We concluded that in GC DLBCL cell lines, in contrast to those of ABC type, functional inhibition of BCL2 family members is usually needed to overcome the resistance to apoptosis to SMO inhibitors. These findings provide a rationale to explore the use of SMO and BCL2 inhibitors as adjuvant therapy for treatment of DLBCL of GC type.
Kranthi Kunkalla; Yadong Liu; Changju Qu; Vasiliki Leventaki; Nitin K Agarwal; Rajesh R Singh; Francisco Vega
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-1
Journal Detail:
Title:  Annals of hematology     Volume:  -     ISSN:  1432-0584     ISO Abbreviation:  Ann. Hematol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107334     Medline TA:  Ann Hematol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Unit 72, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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