Up regulation of Bax and down regulation of Bcl2 during 3-NC mediated apoptosis in human cancer cells

Abstract

BackgroundRecently, we have reported the induction of apoptosis by 2-amino-4-(3-nitrophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-NC) in HepG2, T47D and HCT116 cells with low nano molar IC50 values. In this study, anti-proliferative effects of modified 4-aryle-4H-chromenes derivatives; 2-amino-4-(3-bromophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-BC), 2-amino-4-(3-trifluoromethylphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-TFC) and 2-amino-4-(4,5-methylenedioxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (4, 5-MC) were investigated in three human cancer cell lines. Compared to 3-NC none of the compounds displayed better anti-proliferative effect, although 3-BC appeared somewhat similar. Therefore 3-NC was selected for further studies.Methods and resultsTreatment of HepG2, T47D and HCT116 cells with this compound induced apoptosis as visualized by fluorescence microscopic study of Hoechst 33258 stained cells. Induction of apoptosis was quantified by Annexin V/PI staining using flow cytometry.Western blot analysis also revealed that 3-NC down-regulated the expression of anti-apoptotic protein Bcl2 and up-regulated pro-apoptotic protein Bax, in all of the cell lines. Nonetheless, HepG2 cell line was the most responsive to 3-NC as Bax and Bcl2 showed the most dramatic up and down regulation.ConclusionOur previous finding that 3-NC down regulates Inhibitor of Apoptosis Proteins (IAPs) and the present observation that Bax is upregulated and Bcl2 is down regulated upon 3-NC treatment, this chromene derivative has the potential to overcome chemotherapy resistance caused by up regulation of these proteins.

Vitex Rotundifolia Fractions Induced Apoptosis in Human Breast Cancer T-47D Cell Line via Activation of Extrinsic and Intrinsic Pathway

“…The ratio of pro-apoptotic and anti-apoptotic proteins determines the fate of the cell (An et al, 2004). Up-regulation of Bax and down-regulation of Bcl-2 is usually associated with the cell death and by using the ratio of Bax / Bcl-2 proteins, the fate of cell could be determined (Naseri et al, 2015;Gul-e-Saba et al, 2019). These findings were in parallel with previous studies performed on Vitex rotundifolia and other species of genus Vitex.…”

Biogenic synthesis of AgNPs using Artemisia oliveriana extract and their biological activities for an effective treatment of lung cancer

“…The cell death pathway may include the activation of pro-apoptotic events in the cell, which begin with the increased permeability of mitochondrial membrane caused by Bax and Bak proteins, resulting in the release of cytochrome c, eventually activating CASP9 and then CASP3. In addition, Bcl-2 and Bcl-xL proteins orientate at the surface of endoplasmic reticulum, mitochondria and nucleus, preventing the assembly of Bax and Bak proteins and hence, exhibiting anti-apoptotic activity [36].…”

Changes in the expression of interleukin-10 in myocardial infarction and its relationship with macrophage activation and cell apoptosis

“…Among them, the expression of MCP-1 protein showed a peak, blocking the apoptotic pathway and inhibiting the occurrence of apoptosis [5,21]. However, the ratio of Bcl-2/Bax is closely related to cell apoptosis and survival [6,22]. In this study, the results showed that the number of apoptotic cells in myocardial tissues was increased gradually with prolonged time of infarction, and the expression of Bax protein was also increased gradually, indicating that cardiomyoctyte apoptosis was gradually aggravated with prolonged time of infarction.…”

“…The paraffin tissues were cut into 4 μm slices. Detection of serum IL-10 expression (ELISA) 6 The expression of IL-10 in venous blood of mice was detected by enzyme-linked immunosorbent assay (ELISA). The operations were conducted based on the kit (Andy gene) instructions.…”

“…Myocardial cells undergo apoptosis in addition to ischemia and necrosis in patients with coronary heart diseases [4,5]. Currently, numerous apoptotic proteins are being studied, in which B cell lymphoma-2 (Bcl-2) protein family is the most commonly investigated and is the most classical apoptotic protein [5,6].…”