The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7
human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the
past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing
the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as
anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of
cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2-
hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma
cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line
representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and
specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell
death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time
with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1
phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of
MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.
Keywords: Apoptosis, caspase, human breast cancer adenoma, mitochondria, MCF-7 cell line, MMD, quinazolinone.
Rights & PermissionsPrintExport