Contributions
Abstract: PB1617
Type: Publication Only
Background
In spite of impressive advances in therapeutic approaches, some of the patients with acute lymphoblastic leukemia (ALL) experience a bone marrow relapse with the approximate morbidity and mortality rate of 60%. Since aberrant expression of c-Myc contributes to the unlimited proliferative potential of malignant lymphoblasts, and may confer resistance to chemotherapeutic drugs, inhibition of c-Myc proto-oncogene is proving to be a daunting task for clinicians.
Aims
To assess the anti-tumor effect of c-Myc inhibition in ALL, Nalm-6 cells were treated with the different concentrations of small molecule inhibitor of c-Myc, 10058-F4.
Methods
MTT, Trypan blue, annexin/PI staining, cell cycle analysis, caspase-3 activity, and BrdU cell proliferation assay coupled with analysis of gene expression by using quantitative real-time PCR were applied to examine the effects and molecular mechanisms of action of 10058-F4.
Results
Our results indicated that c-Myc inhibition using 10058-F4 resulted in a considerable growth suppressive effect in Nalm-6 cells mostly through p73-mediated G1 arrest. Moreover, we found that the cytotoxic effects induced in inhibitor-treated cells were likely due to the induction of a caspase 3-mediated apoptosis, as revealed by the increased percentage of Annexin-V and Annexin-V/PI double positive cells in the drug-treated group. Noteworthy, the resulting data showed that combination of 10058-F4 and vincristine produced synergistic anticancer effects and provided an enhanced therapeutic efficacy in pre-B ALL-derived Nalm-6 cells.
Conclusion
Our study not only indicated the potential application of single agent of 10058-F4 in Nalm-6 cells but also outlined the therapeutic efficacy of the inhibitor in combination with the common chemotherapeutic drugs in pre-B ALL.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia, Apoptosis, c-Myc, Targeted therapy
Abstract: PB1617
Type: Publication Only
Background
In spite of impressive advances in therapeutic approaches, some of the patients with acute lymphoblastic leukemia (ALL) experience a bone marrow relapse with the approximate morbidity and mortality rate of 60%. Since aberrant expression of c-Myc contributes to the unlimited proliferative potential of malignant lymphoblasts, and may confer resistance to chemotherapeutic drugs, inhibition of c-Myc proto-oncogene is proving to be a daunting task for clinicians.
Aims
To assess the anti-tumor effect of c-Myc inhibition in ALL, Nalm-6 cells were treated with the different concentrations of small molecule inhibitor of c-Myc, 10058-F4.
Methods
MTT, Trypan blue, annexin/PI staining, cell cycle analysis, caspase-3 activity, and BrdU cell proliferation assay coupled with analysis of gene expression by using quantitative real-time PCR were applied to examine the effects and molecular mechanisms of action of 10058-F4.
Results
Our results indicated that c-Myc inhibition using 10058-F4 resulted in a considerable growth suppressive effect in Nalm-6 cells mostly through p73-mediated G1 arrest. Moreover, we found that the cytotoxic effects induced in inhibitor-treated cells were likely due to the induction of a caspase 3-mediated apoptosis, as revealed by the increased percentage of Annexin-V and Annexin-V/PI double positive cells in the drug-treated group. Noteworthy, the resulting data showed that combination of 10058-F4 and vincristine produced synergistic anticancer effects and provided an enhanced therapeutic efficacy in pre-B ALL-derived Nalm-6 cells.
Conclusion
Our study not only indicated the potential application of single agent of 10058-F4 in Nalm-6 cells but also outlined the therapeutic efficacy of the inhibitor in combination with the common chemotherapeutic drugs in pre-B ALL.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia, Apoptosis, c-Myc, Targeted therapy