In vitro apoptotic mechanism of a novel synthetic Quinazolinyl derivative: Induces caspase-dependent intrinsic pathway on THP-1, leukemia cell line
| Autor: | S.K. Arepalli, L. R. Velatooru, J. Venkateswara Rao, Sridhar Vakamullu, Banda Narsaiah, P Kavin Kennedy |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antineoplastic Agents Apoptosis HL-60 Cells DNA Fragmentation Toxicology Amino Acid Chloromethyl Ketones HeLa 03 medical and health sciences Mice 0302 clinical medicine Cytotoxic T cell Animals Humans THP1 cell line MTT assay Caspase Cells Cultured Cell Proliferation bcl-2-Associated X Protein Membrane Potential Mitochondrial Leukemia biology Chemistry General Medicine biology.organism_classification Molecular biology G1 Phase Cell Cycle Checkpoints In vitro 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Caspases biology.protein Leukocytes Mononuclear Quinazolines DNA fragmentation Poly(ADP-ribose) Polymerases HeLa Cells |
| Zdroj: | Chemico-biological interactions. 280 |
| ISSN: | 1872-7786 |
| Popis: | Several quinazoline derivatives have been found to possess a broad spectrum of biological activities. Previously our research group has synthesized and studied the anti-proliferative effects of N-Decyl-N-(2-Methyl-4-Quinazolinyl) Amine (DMQA). The current study evaluated the cytotoxic and apoptotic properties of DMQA in THP-1 cells. The cytotoxic potential of DMQA was assessed using MTT assay on a panel of cancer cell lines which include HeLa, Mia PaCa-2, A 375, B16-F10, A 549,A 431, U937, THP-1, HL-60 and peripheral blood mononuclear cells (PBMC's). Preliminary data revealed that the highest cytotoxic activity was against THP-1 leukemia cell line (IC50=0.66 μg/ml). The apoptotic properties of DMQA on THP-1 cells were characterized by change in nuclear morphology, DNA fragmentation, reduction of pro-caspases-3, 9, Bax/Bcl-2 levels, cleavage of poly (ADP-ribose) polymerase and cytosolic release of cytochrome c. Further investigation revealed a sub-G1 peak, phosphatidyl serine exposure and loss of mitochondrial membrane potential (MMP) in THP-1 cells. The role of caspases was crucial and was demonstrated by the inhibitors Z-VAD-FMK and Z-DEVD-FMK. Moreover DMQA was markedly less effective in inhibiting the growth of normal cells (PBMC's, IC50 =62.17 μg/ml). Based on the results we suggest that DMQA induced apoptosis via intrinsic pathway and could be a promising anticancer agent. |
| Databáze: | OpenAIRE |
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