LLL-3, a STAT3 inhibitor, represses BCR-ABL-positive cell proliferation, activates apoptosis and improves the effects of Imatinib mesylate.
OBJECTIVE
The chimeric protein BCR-ABL, a constitutively active protein-tyrosine kinase, triggers downstream signalling proteins, such as STAT3, ultimately resulting in the survival of myeloid progenitors in BCR-ABL-positive leukemias. Here, we evaluated the effect of LLL-3, an inhibitor of STAT3 activity, on cell viability and its addictive effects with Imatinib mesylate (IM) treatment in BCR-ABL-positive cells.


METHODS
Viability of cell lines was determined using the WST-1 assay in response to drug treatment, either LLL-3 alone or in conjunction with IM. Annexin V-FITC/PI staining, sub-G1 DNA content and Caspase-3/7 activation assays were performed to evaluate apoptosis.


RESULTS
LLL-3 treatment decreased cell viability, triggered apoptosis and activated Caspases-3/7 in K562 cells. LLL-3 increases IM treatment to inhibited cell viability and activation of apoptosis in BCR-ABL-positive cell lines.


CONCLUSIONS
LLL-3 reduced cell viability and induced apoptosis in K562 cells. Moreover, the observed addictive effects of co-treatment with IM and LLL-3 suggest this combination has therapeutic potential.
Mencalha
Andre Luiz
AL
Instituto de Biofísica Carlos Chagas Filho, CCS, UFRJ, Rio de Janeiro, RJ, Brazil. mencalha@biof.ufrj.br
Du Rocher
B
B
Salles
D
D
Binato
R
R
Abdelhay
E
E
D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*
D000880:Anthraquinones; D000970:Antineoplastic Agents; D001549:Benzamides; C534708:LLL-3 compound; D010879:Piperazines; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D053148:Caspase 3; D053179:Caspase 7