الفهرس | Only 14 pages are availabe for public view |
Abstract The current study evaluated the cytotoxic activity of 11-(1,4- Bisaminopropylpiperazinyl) neocryptolepine (BAPPN), a novel analogue of the natural product alkaloid, neocryptolepine, on hepatocellular carcinoma (HepG2) and colon carcinoma (HCT-116) cell lines, as well, the possible molecular mechanism through which it exerts its cytotoxic activity. BAPPN was synthesized and characterized with FT-IR and NMR spectroscopic. The binding affinity scores of BAPPN for caspase-3 PDB: 7JL7 was −7.836, with an RMSD of 1.483◦ A. InsilIco screening of ADME properties indicated that BAPPN showed promising oral bioavailability records in addition to their high gastrointestinal absorption and blood–brain barrier penetrability. Treatment of HepG2 and HCT-116 cells with BAPPN induced cytotoxicity with IC50 of 3.3 μg/ml for HepG2 cells and IC50 of 23μg /mL for HCT-116 cells. In addition, it induced cell injury and morphological changes in ultracellular structure including, cellular delayed activity, vanishing of membrane blebbing, microvilli, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin autophagosomes. Moreover, BAPPN significantly increased protein expression of Annexin V (apoptotic marker protein) in these cells. Furthermore, BAPPN significantly increased the protein expression of casepase-3 and tumour suppressor protein (P53). However, it significantly reduced the secretion of vascular endothelial growth factor (VEGF) protein into the medium and decreased protein expression of proliferation cellular nuclear antigen (PCNA) and KI67 in HepG2 and HCT-116 cells. This study indicated that BAPPN had cytotoxic action via upregulation of apoptotic proteins against liver and colon cancer cell lines, caspase-3 and P53, and downregulation the expression of proliferative proteins, VEGF, PCNA and KI67. |