Anti-proliferative Effects of Chromones: Potent Derivatives Affecting Cell Growth and Apoptosis in Breast, Bone-marrow and Cervical Cancer Cells

2019 ◽  
Vol 15 (8) ◽  
pp. 883-891
Author(s):  
Syeda Abida Ejaz ◽  
Mariia Miliutina ◽  
Peter Langer ◽  
Aamer Saeed ◽  
Jamshed Iqbal
Keyword(s):  
Cancer Cells ◽  
Chromatin Condensation ◽  
Maximum Growth ◽  
Future Research ◽  
Binding Studies ◽  
Proliferative Effect ◽  
Cervical Cancer Cells ◽  
Apoptotic Effect ◽  
K 562 Cells ◽  
Mcf 7

Background: Previously, we have identified 3,3′–carbonyl–bis(chromones) (1a-h, 5e) and 3–(5–(benzylideneamino)thiozol–3–yl)–2H–chromen–2–ones (7a-j) as potent inhibitors of tissue non-specific alkaline phosphatase (TNAP). The present study was designed to investigate the cytotoxic and pro-apoptotic effect of the said derivatives. Methods: The anti-proliferative effect of the derivatives was investigated in three cancer cell lines i.e., MCF-7, K-562, HeLa and normal BHK21 cells using MTT assay. The pro-apoptotic effect of the most potent derivatives was investigated by using flow cytometry, DAPI and PI staining and DNA binding studies. Results: Among all the screened compounds, 1f, 1d, 1c (from 3,3′–carbonyl–bis(chromones), 7c, 7h and 7i (from 3–(5–(benzylideneamino)thiozol–3–yl)–2H–chromen–2–ones) exhibited remarkable growth inhibitory effects. Compounds 1f and 7c were found to be the most potent cytotoxic derivatives against MCF-7; 1d and 7h inhibited most of the proliferation of K-562 cells, whereas 1c and 7i showed maximum growth inhibition in HeLa cells. The identified compounds exerted lower micromolar potency against the respective cell line with significant selectivity over the normal cells (BHK–21). The identified compounds also induced either G2 or S-phase arrest within the respective cancer cells, chromatin condensation and nuclear fragmentation, as well as maximum interaction with DNA. Conclusions: These results provide evidence that the characteristic chemical features of attached groups are the key factors for their anticancer effects and play a useful role in revealing the mechanisms of action in relation to the known compounds in future research programs.

scholarly journals Adenovirus-Mediated p21(WAF1/SDII/CIP1)Gene Transfer Induces Apoptosis of Human Cervical Cancer Cell Lines

1999 ◽  
Vol 73 (6) ◽  
pp. 4983-4990 ◽  
Author(s):  
Yeou-Ping Tsao ◽  
Shyh-Jer Huang ◽  
Junn-Liang Chang ◽  
Jer-Tsong Hsieh ◽  
Rey-Chen Pong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
High Efficiency ◽  
Recombinant Adenovirus ◽  
Chromatin Condensation ◽  
Adenovirus Vector ◽  
Cervical Cancer Cells ◽  
Apoptotic Effect ◽  
Human Cervical Cancer

ABSTRACT p21(WAF1/SDII/CIP1) (p21) arrests cell growth by inhibiting cyclin-depend kinases. To explore the potential of using p21 for the gene therapy of cervical cancer, we infected human papillomavirus (HPV)-positive cervical cancer cells (HeLa, SiHa, and Z172) and HPV-negative cervical cancer cells (C33A) with recombinant adenovirus encoding p21 cDNA. The results revealed that effective inhibition of cell growth could be achieved by sense p21 adenovirus but not antisense p21 adenovirus infection and occurred through apoptosis as measured by DNA fragmentation and chromatin condensation. Apoptosis was also observed in xenografts of human cervical cancer cells infected with sense p21 adenovirus, as confirmed by in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). The apoptosis was not prevented by overexpression of the bcl-2 transgene. To sum up, the apoptotic effect suggests that p21 should be a tumoricidal agent instead of a tumoristatic agent in preventing cervical cancers. In addition, our report substantiates the combination of the high efficiency of adenovirus vector-mediated gene delivery and the apoptotic effect of p21.

Sensitization of MCF-7 breast cancer cells to the apoptotic effect of estradiol

2006 ◽  
Vol 141 (3) ◽  
pp. 357-360 ◽  
Author(s):  
A. M. Shcherbakov ◽  
Yu. S. Lobanova ◽  
V. A. Shatskaya ◽  
O. V. Onopchenko ◽  
A. V. Gaspar’yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Effect ◽  
Mcf 7

scholarly journals An Insight into the Mechanism of Holamine- and Funtumine-Induced Cell Death in Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5716
Author(s):  
Jelili A. Badmus ◽  
Okobi E. Ekpo ◽  
Jyoti R. Sharma ◽  
Nicole Remaliah S. Sibuyi ◽  
Mervin Meyer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Topoisomerase I ◽  
Caspase 3 ◽  
Steroidal Alkaloids ◽  
Antiproliferative Effects ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Apoptotic Effect ◽  
Mcf 7

Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of Holarrhena. The selective anti-proliferative and cell cycle arrest effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentageTM dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.

Proliferative effect of whey from cows’ milk varying in phyto-oestrogens in human breast and prostate cancer cells

2012 ◽  
Vol 79 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Tina S. Nielsen ◽  
Annika Höjer ◽  
Anne-Maj Gustavsson ◽  
Jens Hansen-Møller ◽  
Stig Purup
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Dietary Treatment ◽  
Human Breast ◽  
Prostate Cancer Cells ◽  
Proliferative Effect ◽  
Significant Difference ◽  
Breast And Prostate Cancer ◽  
Mcf 7

Intake of dietary phyto-oestrogens has received a great deal of attention owing to their potential influence on hormone-sensitive cancers such as breast and prostate cancer. Cows’ milk contains phyto-oestrogens and the content varies according to the composition of the feed and the type and amount of legumes used. In this study we evaluated the proliferative effect of milk (whey) with different phyto-oestrogen content in human breast (MCF-7) and prostate cancer cells (PC-3). Milk was obtained from cows fed either a birdsfoot trefoil-timothy silage based ration (B1) or two different red clover silage based diets (R1 and R2) resulting in total phyto-oestrogen contents of 403, 1659 and 1434 ng/ml for the B1, R1 and R2 diets, respectively. Whey was produced from the milk and added to cell culture medium in concentrations up to 10% for MCF-7 cells and 5% for PC-3 cells. Cell proliferation was measured fluorometrically after 7 d for MCF-7 cells and 5 d for PC-3 cells. There was no significant difference in the proliferative effect of whey from the different dietary treatments at any of the whey concentrations tested. An anti-proliferative effect (P<0·01) of 5 and 10% whey was seen when tested in the presence of 10 pmoestradiol in the medium. This effect was independent of dietary treatment of cows. Whey induced a significant (P<0·01) proliferative response in PC-3 cells independent of dietary treatment. Purified equol in concentrations similar to equol concentrations in milk decreased PC-3 cell proliferation, and therefore the stimulatory effect of whey in PC-3 cells is believed to be mediated by other bioactives than equol. In conclusion, our results suggest that using whey in these proliferation assays, it was not possible to discriminate between milk with high or low levels of phyto-oestrogens.

scholarly journals P121 The anti proliferative effect of Aloin and Aloe emodin on MCF-7 and MDA-MB-231 breast cancer cells

The Breast ◽  
2011 ◽  
Vol 20 ◽  
pp. S22 ◽  
Author(s):  
M.M. Daud ◽  
M.J. Ibrahim ◽  
G.R.A. Froemming ◽  
N.A.H. Hasani
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Proliferative Effect ◽  
Aloe Emodin ◽  
Mcf 7

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 ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Expression Level ◽  
Caspase 8 ◽  
Human Breast ◽  
Caspase 9 ◽  
Anti Cancer ◽  
Apoptotic Effect ◽  
Mcf 7

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.

Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro studyThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (11) ◽  
pp. 1153-1159 ◽  
Author(s):  
Mahéra Al-Akoum ◽  
Sylvie Dodin ◽  
Ali Akoum
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Black Cohosh ◽  
Proliferative Effect ◽  
Dose Dependent ◽  
Mcf 7

Breast cancer cell cultures were exposed to different concentrations of black cohosh, estradiol (E2), and tamoxifen to examine the effect on cell proliferation; cytotoxicity was assessed by using sulforhodamine B (SRB) dye solution. E2 (10−10–10−8 mol/L) markedly stimulated the proliferation of MCF-7 cells (p < 0.01). Tamoxifen stimulated MCF-7 cell proliferation at 10−6 mol/L and 10−5 mol/L (p < 0.005) but inhibited in a dose-dependent fashion the proliferative effect of E2 (p < 0.001). Black cohosh alone did not show any stimulatory effect, but exhibited a cytotoxic effect, which was significant at 103 μg/mL (p < 0.001). Adding black cohosh at 100–103 μg/mL to E2 at 10−9 mol/L also resulted in a dose-dependent inhibition of E2 proliferative effect. Interestingly, the combination of black cohosh (100–103 μg/mL) with increasing tamoxifen concentrations further inhibited MCF-7 cell growth. On MDA-MB-231 cells, neither E2 nor tamoxifen displayed any detectable effect. However, black cohosh inhibited MDA-MB-231 cell proliferation at 103 μg/mL (p < 0.05), and this inhibitory effect was enhanced by increasing tamoxifen concentrations. This study reveals a cytotoxic effect of black cohosh on both estrogen-sensitive and estrogen-insensitive breast cancer cells and a synergism with tamoxifen for inhibition of cancerous cell growth.

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