Anticancer Properties of a New Hybrid Analog AD-013 Combining a Coumarin Scaffold with an α-methylene-δ-lactone Motif

2018 ◽  
Vol 18 (3) ◽  
pp. 450-457 ◽  
Author(s):  
Angelika Dlugosz ◽  
Katarzyna Gach-Janczak ◽  
Jacek Szymanski ◽  
Dariusz Deredas ◽  
Henryk Krawczyk ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Pcr Analysis ◽  
Cytotoxic Activities ◽  
Anticancer Properties ◽  
Apoptotic Genes ◽  
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Background: Coumarin is a natural phytochemical but as such has no medical uses. However, various natural and synthetic coumarin analogs attract attention due to their interesting biological properties. Objective: Here, we evaluated and compared anticancer properties of a new synthetic hybrid compound AD- 013, which integrates a coumarin moiety and an α-methylene-δ-lactone motif, with novobiocin, a natural antibiotic bearing a coumarin scaffold. Methods: Cytotoxic activities of compound AD-013 and novobiocin were assessed by the MTT assay. In order to explore the mechanism of anticancer activity of analog AD-013, we performed quantitative real-time PCR analysis of apoptosis- and cell cycle-related genes. The ability of AD-013 and novobiocin to induce apoptosis and DNA damage was studied by flow cytometry. Results: The cytotoxic activity of this new compound was compared with the activity of a coumarin-based antibiotic novobiocin against two cancer cell lines, MCF-7 and HL-60 and also against normal human cells, MCF- 10A and HUVEC. AD-013 was much more cytotoxic than novobiocin in both cancer cell lines and showed some selectivity against MCF-7 cancer cells as compared with MCF-10A healthy cells. Expression levels of the pro-apoptotic genes significantly increased while the anti-apoptotic genes, were down-regulated for both compounds in both cancer cell lines. </P><P> AD-013 was able to inhibit cell proliferation, generate DNA damage and induce apoptosis. The obtained data showed that this compound caused the cell cycle arrest in subG0/G1 in both cancer cell lines. Conclusion: The new hybrid analog was a much stronger apoptosis inducer than novobiocin and activated the intrinsic pathway of apoptosis.

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
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Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
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Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

scholarly journals Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa)

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Keat Ng ◽  
Latifah Saiful Yazan ◽  
Li Hua Yap ◽  
Wan Abd Ghani Wan Nor Hafiza ◽  
Chee Wun How ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Nanostructured Lipid Carrier ◽  
Cycle Arrest ◽  
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Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P<0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

scholarly journals Cytotoxic Sterols from Philippine Mushrooms

2020 ◽  
Vol 32 (5) ◽  
pp. 1197-1202
Author(s):  
Consolacion Y. Ragasa ◽  
Glenn G. Oyong ◽  
Maria Carmen S. Tan ◽  
Mariquit M. De Los Reyes ◽  
Maria Ellenita G. De Castro
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Dermal Fibroblast ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cell Viability Assay ◽  
Ic50 Values ◽  
Ht 29 ◽  
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Ergosterol peroxide (1) and ergosterol (2) were commonly isolated as the major compounds of Philippine mushrooms. Sterols 1 and 2 from the dichloromethane extract of Geastrum triplex and Termitomyces clypeatus, respectively, were evaluated for their cytotoxic activities against four human cancer cell lines, viz., breast cancer (MCF-7), colon cancer (HT-29), leukemia (THP-1), and small lung cell carcinoma (H69PR), and a human normal cell line, human dermal fibroblast-neonatal (HDFn), using the PrestoBlue® cell viability assay. Compounds 1 and 2 exhibited the strongest activities against HT-29 with IC50 values of 1.79 and 2.98 μg/mL, respectively, while Zeocin gave an IC50 of 4.89 μg/mL. These compounds also exhibited strong antiproliferative effects against MCF-7 with IC50 values of 4.13 for 1 and 4.20 μg/mL for compound 2, comparable to Zeocin with IC50 = 3.68 μg/mL. Only moderate cytotoxicity resulted when compounds 1 and 2 were tested against H69PR with IC50 values of 7.78 and 6.83 μg/mL, respectively, while Zeocin exhibited an IC50 of 9.81 μg/mL. Furthermore, compounds 1 and 2 showed no effects against THP-1 (IC50 > 100 μg/mL), while Zeocin showed an IC50 of 4.73 μg/mL. Although compounds 1 and 2 have been reported to exhibit different bioactivities in previous studies, the cancer cell lines tested and/or the polarities of the solvents for extraction varied. Therefore, comparisons of the cytotoxic activities of compounds 1 and 2 with earlier studies could not be made extensively.

scholarly journals ­Chemical profiling and biological activity of Peperomia blanda (Jacq.) Kunth

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4839 ◽  
Author(s):  
Wafa M. Al-Madhagi ◽  
Najihah Mohd Hashim ◽  
Nasser A. Awad Ali ◽  
Abeer A. Alhadi ◽  
Siti Nadiah Abdul Halim ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Radical Scavenging ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Standard Drug ◽  
Chemical Profiling ◽  
First Time ◽  
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Background Peperomia belongs to the family of Piperaceae. It has different uses in folk medicine and contains rare compounds that have led to increased interest in this genus. Peperomia blanda (Jacq.) Kunth is used as an injury disinfectant by Yemeni people. In addition, the majority of Yemen’s population still depend on the traditional remedy for serious diseases such as cancer, inflammation and infection. Currently, there is a deficiency of scientific evidence with regards to the medicinal plants from Yemen. Therefore, this study was performed to assess the chemical profile and in vitro antioxidant and cytotoxic activities of P. blanda. Methods Chemical profiling of P. blanda was carried out using gas chromatography mass spectrometry (GCMS) followed by isolation of bioactive compounds by column chromatography. DPPH• and FRAP assays were used to evaluate antioxidant activity and the MTT assay was performed to estimate the cytotoxicity activity against three cancer cell lines, namely MCF-7, HL-60 and WEHI-3, and three normal cell lines, MCF10A, WRL-68 and HDFa. Results X-ray crystallographic data for peperomin A is reported for the first time here and N,N′-diphenethyloxamide was isolated for the first time from Peperomia blanda. Methanol and dichloromethane extracts showed high radical scavenging activity with an IC50 of 36.81 ± 0.09 µg/mL, followed by the dichloromethane extract at 61.78 ± 0.02 µg/mL, whereas the weak ferric reducing activity of P. blanda extracts ranging from 162.2 ± 0.80 to 381.5 ± 1.31 µg/mL were recorded. In addition, petroleum ether crude extract exhibited the highest cytotoxic activity against all the tested cancer cell lines with IC50 values of 9.54 ± 0.30, 4.30 ± 0.90 and 5.39 ± 0.34 µg/mL, respectively. Peperomin A and the isolated mixture of phytosterol (stigmasterol and β-sitosterol) exhibited cytotoxic activity against MCF-7 and WE-HI cell lines with an IC50 of (5.58 ± 0.47, 4.62 ± 0.03 µg/mL) and (8.94 ± 0.05, 9.84 ± 0.61 µg/mL), respectively, compared to a standard drug, taxol, that has IC50 values of 3.56 ± 0.34 and 1.90 ± 0.9 µg/mL, respectively. Conclusion The activities of P. blanda extracts and isolated compounds recorded in this study underlines the potential that makes this plant a valuable source for further study on anticancer and antioxidant activities.

scholarly journals Synthesis, Characterization, and In Vitro Cancer Cell Growth Inhibition Evaluation of Novel Phosphatidylcholines with Anisic and Veratric Acids

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2022 ◽  
Author(s):  
Marta Czarnecka ◽  
Marta Świtalska ◽  
Joanna Wietrzyk ◽  
Gabriela Maciejewska ◽  
Anna Gliszczyńska
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Organism ◽  
Cancer Cell Growth ◽  
Anticancer Properties ◽  
Health Promoting ◽  
Phenolcarboxylic Acids ◽  
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Phenolic acids and its methoxy derivatives are known to induce caspase-mediated apoptosis activity and exhibit cytotoxic effect towards various cancer cell lines. However, their low stability and poor bioavailability in the human organism extensively restrict the utility of this group of compounds as anticancer and health-promoting agents. In this report, a series of eight novel phosphatidylcholines (3a-b, 5a-b, 7a-b, 8a-b) containing anisic or veratric acids (1a-b) at sn-1 and/or sn-2 positions were synthesized. The phenoylated phospholipids were obtained in good yields 28–66%. The structures of novel compounds were determined by their spectroscopic data. All synthesized compounds were evaluated for their antiproliferative activity towards six cancer cell lines and normal cell line Balb/3T3. Lipophilization of phenolcarboxylic acids significantly increased their anticancer properties. The asymmetrically substituted phenoylated phosphatidylcholines exhibited higher antiproliferative effect than free acids. Lysophosphatidylcholine (7b) effectively inhibited the proliferation of human leukaemia (MV4-11), breast (MCF-7), and colon (LoVo) cancer cell lines at concentrations of 9.5–20.7 µm and was from 19 to 38-fold more active than corresponding free veratric acid. The conjugation of anisic/veratric acids with the phosphatidylcholine have proved the anticancer potential of these phenolcarboxylic acids and showed that this type of lipophilization is an effective method for the production of active biomolecules.

scholarly journals In Vitro Evaluation of Cytotoxic Activities of Marketed Herbal Products in Ghana

2018 ◽  
Vol 23 ◽  
pp. 2515690X1879072 ◽  
Author(s):  
Sylvester Languon ◽  
Isaac Tuffour ◽  
Emmanuel Ekow Quayson ◽  
Regina Appiah-Opong ◽  
Osbourne Quaye
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Jurkat Cells ◽  
Total Phenolic ◽  
Cytotoxic Activities ◽  
Hep G2 ◽  
Herbal Products ◽  
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There are numerous herbal products on the Ghanaian market that are purported to cure various ailments, including cancer. However, scientific investigations on efficacy and toxicity of most of these products are not done. The aim of the study was to assess the anticancer potentials of herbal products on the Ghanaian market. Antiproliferative effects of Kantinka BA (K-BA), Kantinka Herbaltics (K-HER), Centre of Awareness (COA), a stomach (STO) and multicancer (MUT) product were evaluated in vitro using liver (Hep G2), breast (MCF-7), prostate (PC-3 and LNCaP), and blood (Jurkat) cancer cell lines. Cytotoxicity of the medicinal products was assessed using tetrazolium-based colorimetric assay, and total phenolic content and antioxidant activity of the products were determined using Folin-Ciocalteau and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, respectively. Phytochemical screening resulted in the detection of terpenoids and flavonoids in most of the products, and alkaloids were detected in only MUT. Tannins were absent from all the products. The highest and lowest concentrations of phenolics were recorded for MUT and K-BA, respectively. The highest and lowest antioxidant activities were measured for MUT and K-HER, respectively. Only 2 products (STO and MUT) were cytotoxic to Hep G2 cells; with MUT being the only product that was cytotoxic to MCF-7 cells. All but K-BA were cytotoxic to PC-3 cells, while all products except K-HER were cytotoxic to LNCaP and Jurkat cells. The study thus confirms that the herbal products have selective cytotoxic activities against the tested cancer cell lines. However, comprehensive toxicity studies must be conducted to establish their safety.

scholarly journals Antiproliferative effect of the Red Sea cone snail, Conus geographus

2020 ◽  
Vol 19 (3) ◽  
pp. 577-581
Author(s):  
Najla Ali Alburae ◽  
Afrah Eltayeb Mohammed
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Red Sea ◽  
Hepg2 Cells ◽  
Cancer Cell Lines ◽  
Antiproliferative Effect ◽  
Cone Snail ◽  
Ic50 Values ◽  
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Purpose: To investigate the antiproliferative effect of the Red Sea cone snail, Conus geographus, against 4 MCF-7 (breast), MDA-MB-231 (epithelial human breast), HepG2 (hepatocellular) and SKOV-3 (ovarian) cancer cell lines. Methods: Extraction of Red Sea cone snail sample with a mixture of CH2Cl2 and CH3OH (1:1, v/v) yielded 0.55 g of a green viscous material. The cytotoxic effects of the organic extract against the cancer cell lines were determined using cell proliferation (MTT) assay, and the half-maximal concentration (IC50) values measured. The effect of the crude extract on the cell cycle of the HepG-2 was determined by flow cytometry. Results: The extract produced significant inhibitory effects against SKOV-3, MDA-MB-231, MCF-7 and HepG2, with IC50 values of 22.7 ± 2.2, 68.7 ± 6.2, 47 ± 4.2 and 19 ± 2.1 μg/mL, respectively. Cell cycle analysis revealed that the extract enhanced accumulation of HepG2 cells in the Go/G1 phase, at a level of 23.4 and 24.1 % at IC50 (19 μg/mL) and ½ IC50 (9.5 μg/mL), respectively, when compared to the untreated cells. Conclusion: These results indicate that C. geographus extract exhibits potent cytotoxic effect against HepG2 cells via a mechanism involving G0/G1 cell cycle arrest. Thus, C. geographus is a potential source of a new anti-cancer agent. Keywords: Conus geographus, Marine invertebrate, HepG2, Antiproliferation

The Effect of a Ferrocene Containing Camphor Sulfonamide DK-164 on Breast Cancer Cell Lines

2019 ◽  
Vol 19 (15) ◽  
pp. 1874-1886
Author(s):  
Maria Schröder ◽  
Shazie Yusein-Myashkova ◽  
Maria Petrova ◽  
Georgi Dobrikov ◽  
Mariana Kamenova-Nacheva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Regulatory Pathways ◽  
Cycle Arrest ◽  
Mcf 7

Background: Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process. Methods: We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164 on two breast cancer and one breast non-cancer cell lines. The cytotoxic effects were evaluated using the standard MTT-dye reduction and clonogenic assays. The apoptotic or autophagic effects were evaluated by Annexin v binding or LC3 puncta formation assays respectively. Cell cycle arrest was determined using flow cytometry. Western blot and immunofluorescent analyses were used to estimate the localization and cellular distribution of key regulatory factors NFκB and p53. Results: Compound DK-164 has well pronounced cytotoxicity greater to cancer cells (MDA-MB-231 and MCF-7) compared to non-cancerous (MCF-10A). IC50 of the substance caused a cell cycle arrest in G1 phase and induced apoptosis up to 24 hours in both tumor cells, although being more pronounced in MCF-7, a functional p53 cell line. Treatment with IC50 concentration of the compound provoked autophagy in both tumor lines but is better pronounced in the more aggressive cancer line (MDA-MB-231). Conclusion: The tested compound DK-164 showed promising properties as a potential therapeutic agent.

scholarly journals Biscembranoids from the Marine Sponge Petrosia Nigricans

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Nguyen Xuan Nhiem ◽  
Ngo Van Quang ◽  
Chau Van Minh ◽  
Dan Thi Thuy Hang ◽  
Hoang Le Tuan Anh ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Marine Sponge ◽  
Methanol Extract ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Mcf 7

One new biscembranoid, petronigrione (1), and five known compounds, methyl tortuoate B (2), lobophytone U (3), lobophytone H (4), (24 S)-ergostane 3β,5α,6β,25tetraol-25-monoacetate (5), and (24 S)-ergostane-1β,3β,5α,6β,25-pentaol-25-monoacetate (6), were isolated from the methanol extract of the marine sponge Petrosia nigricans. Their structures were established on the basis of spectral and chemical evidence. The cytotoxicity of all compounds was evaluated by MTT assay on four human cancer cell lines, HepG2, KB, LU-1, and MCF-7. Compounds 1 and 2 exhibited moderate cytotoxic activities on the four human cancer cell lines with IC50 values ranging of 20.7 - 28.9 μg/mL.

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