scholarly journals Anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on MCF-7 human breast cancer cell

2021 ◽  
Author(s):  
Maryam Ghaffari ◽  
Dariush Shanehbandi ◽  
Solmaz Sarhadi ◽  
Mina Hanifeh Ahagh ◽  
Mahsa Maleki Moghaddam ◽  
...  

Background: Quinoline and its derivatives display various biological activities based on versatility in designing a new drug class for medicinal applications. Hence, synthesizing innovative and varied derivatives of quinoline has gained considerable attention among chemists and biologists. This study evaluated the anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells. Methods: The anti-proliferative effect of tetrahydrobenzo[h]quinoline was studied via MTT [3 0-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assays. A quantitative and qualitative study of apoptosis was carried out via flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Quantitative real-time PCR (qPCR) and immunoblotting analysis were employed to identify the expression level of genes and proteins involved in the apoptosis signaling pathway. Results: The synthesized compound reduced 50% of cell growth at concentrations of 10 and 7.5 µM during 24 and 48h, respectively, and induced apoptosis up to 30% in MCF-7 cancer cells. Regarding the gene expression level, Bcl-2 displayed considerable alleviation, whereas Bax expression increased significantly. Despite the remarkable increase in caspase 9 expression, there was no noticeable difference in the caspase 8 expression in treated cells compared to the control group. Western blotting data showed that the protein expression level of Bcl-2, pro-caspase 8, and 9 reduced. The protein content of Bax, cleaved-caspase 8, and 9 increased significantly, of which the protein level of cleaved-caspase 9 exhibited a tremendous rise in the treated group. Conclusion: The newly synthesized tetrahydrobenzo[h]quinoline can be a promising organic compound for cancer treatment if its anti-cancer effect investigates by other types of breast cancer cells. In vivo studies should be used to investigate the anti-cancer efficiency of this compound.

2016 ◽  
Vol 2 (4) ◽  
pp. 94 ◽  
Author(s):  
Sarojini S. ◽  
Senthilkumaar P. ◽  
Ramesh V.

The ethanol extract of Mikania glomerata has anti-proliferative effect on the human breast cancer cell lines. The object of the present work is to investigate the anti-cancer effect of Mikania glomerata ethanolic extract on breast cancer. Soxlet fractions using crude ethanolic extract of Mikania glomerata was prepared by standard extraction protocols. To check the antiproliferative effect of this extract, the extract chosen was tested for cell viability on the breast cancer cells MCF 7 in different concentrations. Cell viability was evaluated by MTT assay for 24 hour and 48 hours. The LD50 value was calculated and different morphometric assays were performed with the effective dose of the extract. The effect of the extract on the normal cell was evaluated as well. Cell proliferation, cell cycle, Clonogenic survival, Apoptosis and MTT assays were performed. The ethanolic extract showed a dose-dependent and time dependent inhibition on cell proliferation in the breast cancer cell lines. It showed low cytotoxicity in the normal cells and inhibited cellular adhesion and wound healing in treated cancer cells. The present study suggests that the leaf extract from Mikania glomerata induces anticancer effect on the breast cancer cells. Further study might help to confirm it as an anti-cancer drug.


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3623 ◽  
Author(s):  
Anjugam Paramanantham ◽  
Min Jeong Kim ◽  
Eun Joo Jung ◽  
Hye Jung Kim ◽  
Seong-Hwan Chang ◽  
...  

Anthocyanins isolated from Vitis coignetiae Pulliat (Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-κB which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-κB and p-IκB and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-κB and p-IκB in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-α treatment, AIMs augmented CDDP efficacy with inhibition of NF-κB activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-κB activity of MCF-7 cells that show relative intrinsic CDDP resistance.


2015 ◽  
Vol 6 (3) ◽  
pp. 995-1000 ◽  
Author(s):  
Jun Chen ◽  
Yuxin Duan ◽  
Xing Zhang ◽  
Yu Ye ◽  
Bo Ge ◽  
...  

Genistein is an estrogenic soy-derived compound belonging to the isoflavone class and shows anti-cancer effects.


2020 ◽  
pp. 1-5
Author(s):  
Oyindamola Vivian Ojulari ◽  
Jong-Beom Chae ◽  
Seul Gi Lee ◽  
Kyoungjin Min ◽  
Taeg Kyu Kwon ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1942-1942
Author(s):  
Xiaofeng Jiang ◽  
Yan-Lin Guo ◽  
Michael E. Bromberg

Abstract Tissue factor (TF) is a transmembrane glycoprotein that initiates blood coagulation when complexed with factor VIIa (FVIIa). TF is constitutively expressed by a variety of tumor cells. Recently, TF has been shown to induce cellular signaling and promote tumor growth, angiogenesis, and metastasis. We showed previously that formation of TF-FVIIa-Factor Xa (FXa) complex induces cellular signaling in the Adr-MCF-7 cell line, a multidrug-resistant subline of the human breast cancer cell line, MCF-7 (Jiang et al. J. Thromb Haemost2: 2004; 93–101). This cell line has high endogenous expression of TF. Treatment of the Adr-MCF-7 cells with the combination of FVIIa (10 nM) and FX (150 nM) induces phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), whereas no increase in the basal level of phosphorylation of these proteins occurs with treatment of the cells with FVIIa (10 nM) alone. In the present study, we investigated whether TF-FVIIa-induced signaling might alter apoptosis in human breast cancer cells. Apoptosis of the Adr-MCF-7 cells was induced by serum starvation for 5–7 days. Treatment of the cells with the combination of FVIIa (10 nM) and FX (150 nM), reduced apoptosis of the cells by nearly 50% compared with untreated, control cells using an ELISA that detects histone-DNA fragments. In contrast, FVIIa (10 nM) alone did not significantly prevent apoptosis. Pre-treatment of the Adr-MCF-7 cells with hirudin did not inhibit the anti-apoptotic effect of the combination of FVIIa and FX, whereas this effect could be completely blocked by either U0126 (10 μM), which inhibits p44/42 MAPK phosphorylation, or LY294002 (50 μM), which inhibits PKB phosphorylation. In addition, treatment of the Adr-MCF cells with the combination of FVIIa and FX led to a 50% increase in the level of the anti-apoptotic protein, survivin, compared with untreated cells by Western blot analysis. Results from this study indicate that formation of TF-FVIIa-FXa complex prevents apoptosis of breast cancer cells by a thrombin-independent pathway. Moreover, the anti-apoptotic effect of this signaling pathway involves both phosphorylation of p44/42 MAPK and PKB and might be mediated in part by an increase in cell survivin levels.


2006 ◽  
Vol 96 (08) ◽  
pp. 196-201 ◽  
Author(s):  
Xiaofeng Jiang ◽  
Yan Guo ◽  
Michael Bromberg

Summary Tissue factor (TF) is a transmembrane glycoprotein that initiates blood coagulation when complexed with factorVIIa (FVIIa).TF is constitutively expressed ina variety of tumor cells and has been shown to playa role in cellular signaling and tumor progression. In this study, we investigated the effect of TF-FVIIa mediated signaling on apoptosis in human breast cancer cells. Apoptosis was induced by prolonged serum starvation and studied using the Adr-MCF-7 cell line, which has high endogenous TF expression. Treatment of the cells with the combination of FVIIa (10 nM) and FX (150 nM), reduced apoptosis by nearly 50% compared with untreated, control cells using an ELISA that detects histone-DNA fragments. In contrast, FVIIa (10 nM) alone did not significantly prevent apoptosis. Pretreatment of the Adr-MCF-7 cells with hirudin, a specific thrombin inhibitor, did not inhibit the anti-apoptotic effect of the combination of FVIIa and FX, whereas this effect could be abrogated by inhibition of phosphorylation of either p44/42 mitogen-activated protein kinase (MAPK) or protein kinaseB (PKB/Akt). In addition, treatment of theAdr-MCF-7 cells with the combination of FVIIa and FX led to a 30-50% increase in the level of the anti-apoptotic protein, survivin, compared with untreated cells usingWestern blot analysis. These results indicate that formation of TF-FVIIa-FXa complex prevents apoptosis in breast cancer cells by a thrombin-independent pathway. Moreover, the anti-apoptotic effect of this signaling pathway involves phosphorylation of both p44/42 MAPK and PKB/Akt and might be mediated in part by an increase in cell survivin levels.


Sign in / Sign up

Export Citation Format

Share Document