scholarly journals Characterization of a novel FADS2 transcript variant: implications for D6D activity regulation in cells

2021 ◽  
pp. 1-10
Author(s):  
Kristin A. Marks ◽  
Maria F. Fernandes ◽  
Kalsha H. Diaguarachchige De Silva ◽  
Michelle V. Tomczewski ◽  
Ken D. Stark ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Gene Mutations ◽  
Cancer Cell Lines ◽  
Dominant Negative ◽  
Hek293 Cells ◽  
Activity Regulation ◽  
Apoptosis Regulation ◽  
Transcriptional Start Sites ◽  
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Delta-6-desaturase (D6D) activity is deficient in MCF-7 and other cancer cell lines, but it is not explained by FADS2 gene mutations. This deficient activity was not ameliorated by induction of the FADS2 gene; therefore, we hypothesized that some of the induced FADS2 transcript variants (tv) may play a negative regulatory role. FADS2_tv1 is the reference FADS2 tv, coding for full-length D6D isoform 1 (D6D-iso1), and alternative transcriptional start sites result in FADS2_tv2 and FADS2_tv3 variants encoding D6D-iso2 and D6D-iso3 isoforms, respectively, which lack the catalytically critical N-terminal domain. In MCF-7 cells, FADS2_tv2 and FADS2_tv3 were expressed at significantly higher levels than FADS2_tv1. Overexpression of FADS2_tv2 in HEK293 cells confirmed that D6D-iso2 is non-functional, and co-transfection demonstrated a dominant-negative role for D6D-iso2 in D6D-iso1 activity regulation. FADS2_tv2 was expressed at higher levels than FADS2_tv1 in HeLa, MDA-MB-435, MCF-10 A, and HT-29 cells, but at lower levels in A549, MDA-MB-231, and LNCaP cells. Overexpression studies indicated roles for FADS2 variants in proliferation and apoptosis regulation, which were also cell-line specific. Increased FADS2_tv2 expression provides a new mechanism to help explain deficient D6D activity in MCF-7 and other cancer cell lines, but it is not a hallmark of malignant cells.

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

Novel Conjugated Quinazolinone-Based Hydroxamic Acids: Design, Synthesis and Biological Evaluation

2020 ◽  
Vol 16 ◽  
Author(s):  
Tran Khac Vu ◽  
Nguyen Thi Thanh ◽  
Nguyen Van Minh ◽  
Nguyen Huong Linh ◽  
Nguyen Thi Phương Thao ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Cell Lines ◽  
Cancer Cell ◽  
Hdac Inhibitors ◽  
Cancer Cell Lines ◽  
Hydroxamic Acids ◽  
Biological Evaluation ◽  
Hdac Inhibition ◽  
Ic50 Value ◽  
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Background: Target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development. Histone deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. Aims: This study aims at developing novel HDAC inhibitors bearing conjugated quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. Method: A series of novel N-hydroxyheptanamides incorporating conjugated 6-hydroxy-2 methylquinazolin-4(3H)- ones (15a-l) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7 and SKLu-1. Molecular simulations were finally performed to gain more insight into the structure-activity. relationships. Results: It was found that among novel conjugated quinazolinone-based hydroxamic acids synthesized, compounds 15a, 15c and 15f were the most potent, both in terms of HDAC inhibition and cytotoxicity. Especially, compound 15f displayed up to nearly 4-fold more potent than SAHA (vorinostat) in terms of cytotoxicity against MCF-7 cell line with IC50 value of 1.86 µM, and HDAC inhibition with IC50 value of 6.36 µM. Docking experiments on HDAC2 isozyme showed that these compounds bound to HDAC2 with binding affinities ranging from -10.08 to -14.93 kcal/mol compared to SAHA (-15.84 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward SKLu-1than MCF-7 and HepG-2. Conclusion: The resesrch results suggest that some hydroxamic acids could emerge for further evaluation and the results are well served as basics for further design of more potent HDAC inhibitors and antitumor agents.

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 Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3923
Author(s):  
Adel A.-H. Abdel-Rahman ◽  
Amira K. F. Shaban ◽  
Ibrahim F. Nassar ◽  
Dina S. EL-Kady ◽  
Nasser S. M. Ismail ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

scholarly journals Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3041
Author(s):  
Xiaohan Hu ◽  
Sheng Tang ◽  
Feiyi Yang ◽  
Pengwu Zheng ◽  
Shan Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Structure Activity ◽  
Excellent Activity ◽  
Ic50 Values ◽  
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Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

scholarly journals Factors modulating integrin Beta I expression on the breast cancer cell lines MCF-7 and MDA-MB-231

2000 ◽  
Vol 2 (S1) ◽  
Author(s):  
CJ Pogson ◽  
CMW Chan ◽  
L-A Martin ◽  
GPH Gui ◽  
M Dowsett
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

scholarly journals Analyzing Cytotoxic and Apoptogenic Properties ofScutellaria litwinowiiRoot Extract on Cancer Cell Lines

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Zahra Tayarani-Najaran ◽  
Seyed Ahmad Emami ◽  
Javad Asili ◽  
Alireza Mirzaei ◽  
Seyed Hadi Mousavi
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Cancer Cell ◽  
Methylene Chloride ◽  
Apoptotic Cell ◽  
Malignant Cell ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Mcf 7

TheScutellariaspecies (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian speciesS. litwinowiihave not yet been conducted.The cytotoxic properties of total methanol extract ofS. litwinowiiand its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak).Scutellaria litwinowiiinhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions ofS. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC50values of this fraction against AGS, HeLa, MCF-7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4μg/ml, respectively.Scutellaria litwinowiiinduced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved inS. litwinowiitoxicity.Scutellaria litwinowiiexerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.

scholarly journals In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Luqman Nordin ◽  
Arifah Abdul Kadir ◽  
Zainul Amiruddin Zakaria ◽  
Rasedee Abdullah ◽  
Muhammad Nazrul Hakim Abdullah
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
In Vitro Investigation ◽  
Ardisia Crispa ◽  
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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 ◽  
Mcf 7

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.

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