Contributions
Abstract: PB1713
Type: Publication Only
Background
The c-Myc proto-oncogene, an important regulator of cell proliferation, is amplified in many tumor types and has been linked to both the development and progression of a wide range of human cancers spanning from solid tumors to leukemia. Interest into c.Myc targeted therapy has elevated by the intertwining between acquisition of chemoresistant phenotype and the aberrant expression of c.Myc in leukemia patients.
Aims
This study was aimed to investigate the anti-cancer effects of 10058-F4, a potent small-molecule inhibitor of c-Myc, in acute promyelocytic leukemia (APL).
Methods
APL-derived NB4 cells were subjected to the increasing concentrations of 10058-F4 and then, the cytotoxic effect of the inhibitor was studied using trypan blue, Annexin/PI, MTT, caspase-3 activity, and BrdU cell proliferation assays. Moreover, gene expression analysis by using quantitative real-time PCR was applied to investigate the molecular mechanisms of action of 10058-F4.
Results
We found that the cytotoxic effects of the inhibitor, as revealed by the decreased cell viability and metabolic activity, were mediated through induction of apoptotic pathway in NB4 cells. The resulting data also outlined that inhibitor-induced apoptosis was accompanied by the elevated Bax/Bcl-2 molecular ratio and the enhanced augmentation of caspase-3 activity. Moreover, we found that abrogation of c.Myc using 10058-F4 resulted in a considerable increase in the mRNA expression levels of cyclin-dependent kinase inhibitors p21 and p27, which was in agreement with the induction of G1 cell cycle arrest in APL-derived NB4 cells.
Conclusion
The present study revealed that c-Myc inhibition using a potent small-molecule inhibitor affects multiple cellular activities in NB4 cells and represents a novel promising anti-leukemic approach in APL treatment.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Promyelocytic Leukemia, Apoptosis, c-Myc, P21
Abstract: PB1713
Type: Publication Only
Background
The c-Myc proto-oncogene, an important regulator of cell proliferation, is amplified in many tumor types and has been linked to both the development and progression of a wide range of human cancers spanning from solid tumors to leukemia. Interest into c.Myc targeted therapy has elevated by the intertwining between acquisition of chemoresistant phenotype and the aberrant expression of c.Myc in leukemia patients.
Aims
This study was aimed to investigate the anti-cancer effects of 10058-F4, a potent small-molecule inhibitor of c-Myc, in acute promyelocytic leukemia (APL).
Methods
APL-derived NB4 cells were subjected to the increasing concentrations of 10058-F4 and then, the cytotoxic effect of the inhibitor was studied using trypan blue, Annexin/PI, MTT, caspase-3 activity, and BrdU cell proliferation assays. Moreover, gene expression analysis by using quantitative real-time PCR was applied to investigate the molecular mechanisms of action of 10058-F4.
Results
We found that the cytotoxic effects of the inhibitor, as revealed by the decreased cell viability and metabolic activity, were mediated through induction of apoptotic pathway in NB4 cells. The resulting data also outlined that inhibitor-induced apoptosis was accompanied by the elevated Bax/Bcl-2 molecular ratio and the enhanced augmentation of caspase-3 activity. Moreover, we found that abrogation of c.Myc using 10058-F4 resulted in a considerable increase in the mRNA expression levels of cyclin-dependent kinase inhibitors p21 and p27, which was in agreement with the induction of G1 cell cycle arrest in APL-derived NB4 cells.
Conclusion
The present study revealed that c-Myc inhibition using a potent small-molecule inhibitor affects multiple cellular activities in NB4 cells and represents a novel promising anti-leukemic approach in APL treatment.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Promyelocytic Leukemia, Apoptosis, c-Myc, P21