e12550 Background: Despite intensive efforts, a validated targeted therapy for triple-negative breast cancer (TNBC) remains elusive. One of the most frequent genetic alterations identified in TNBC is amplification of the MYC gene which is found in > 60% of samples. The aim of this study was therefore to investigate the potential value of targeting MYC activation with the recently identified selective and high-affinity low molecular weight MYC inhibitor MYCMI-6, for the treatment of TNBC. Methods: Cell viability was determined using the MTT assay and apoptosis by flow cytometry using annexin V-propidium iodide staining. Results: Based on a panel of 13 breast cancer cell lines, IC50 values for inhibition of proliferation by MYCMI-6 ranged from 1.2 to 96.7 μM. Significantly lower IC50 values were found for TNBC than for non-TNBC cell lines (p = 0.04), i.e., TN cell lines were more sensitive to MYCMI-6 than non-TN cell lines. IC50 values for MYCMI-6 were compared with 2 older MYC inhibitors, i.e., 10058-F4 and KJ Pyr 9. Of these 3 inhibitors, the lowest IC50 values were found for MYCMI-6, i.e., MYCMI-6 was the most sensitive of the 3 inhibitors investigated (p < 0.0001 for MYCMI-6 versus both 10058-F4 and KJ Pyr 9). In addition to inhibiting cell proliferation, MYCMI-6 was found to induce apoptosis in a time and concentration-dependent manner in multiple breast cancer cell lines. A significant correlation was found between MYCMI-6 IC50 and induction of apoptosis ((p = 0.0499, r 2= 0.9026, n = 4), i.e., the lower the IC50 value, the greater the number of apoptotic cells present. This finding suggests that MYCMI-6 decreases cell proliferation by inducing apoptosis. Conclusions: We conclude that the MYC targeting compound, MYCMI-6 is a potential new treatment for TNBC.
Heterogeneous responses of triple negative breast cancer cell lines to radiation and pharmacological treatments
