Alexander Fisch, Chelsea Reiber, William Schroeder, Robert Smart and Osman V Patel*
Background/objective: Chemotherapy remains the mainstay therapy for the most intrusive-type of breast carcinoma, triple-negative breast cancer (TNBC) that has a higher tendency for visceral metastases, relapses, and poor prognoses. It is well recognized that the reactivation of a ribonucleoprotein enzyme, telomerase is among the key determinants of breast carcinogenesis, cellular immortalization and metastatic progression. Therefore, our objectives were to assess (i) short- and (ii) long-term effects of a novel anthranilic acid (GV6) developed at our institute and compare it to a known analogue, BIBR1532 on TNBC (MDA-MB 231) and non-TNBC (MCF-7) cells.
Methods: Seeded TNBC and non-TNBC flasks were supplemented with 25 µM of either BIBR 1532 or GV6 or solvent (DMSO) alone for 14 (Short-term) or 27 (Long-term) days. Trypan-blue dye exclusion test was utilized to determine viable cells, senescence-associated β-galactosidase activity was employed to detect senescent cells and qPCR was used to quantitate transcript abundance.
Results: Cell viability assay revealed that short- and long-term growth inhibitions of TNBC and non-TNBC cells were comparable between BIBR1532 and GV6. Cytochemical detection of βGalactosidase demonstrated that GV6 was equally effective in inducing replicative senescence in treated TNBC and non-TNBC cells. Short- and long-term regimen of BIBR1532 and GV6 showed similar drug-induced downregulation of hTERT in TNBC and non-TNBC cells.
Conclusion: Results indicate that GV6 is an equally potent inhibitor of hTERT that induces growth impedance and triggers senescence in TNBC, as well as non-TNBC cells and merits further studies for improved treatment options.
