scholarly journals Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone-Thienopyrimidine Derivatives in HepG2 and MCF-7 Cell Lines

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Ghada M. Safwat ◽  
Kamel M. A. Hassanin ◽  
Eman T. Mohammed ◽  
Essam Kh. Ahmed ◽  
Mahmoud R. Abdel Rheim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Docking ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Structural Features ◽  
Anticancer Activities ◽  
Cycle Arrest ◽  
Hybrid Molecules ◽  
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Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC50 of the two compounds (3b and 3g) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only 3b and 3g had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds (3a-e and 3g) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress via increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the 3a, 3b, and 3g in HepG2 and 3b and 3g in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( R 2 = 0.531 ; P = 0.001 ) and MCF-7 ( R 2 = 0.219 ; P = 0.349 ) cell lines. The results of molecular docking analysis of 3a-g into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds 3a-g showed 2 violations from Lipinski’s rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds 3a-g than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations.

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 ◽  
Mcf 7

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 ◽  
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.

scholarly journals Peptide SA12 inhibits proliferation of breast cancer cell lines MCF-7 and MDA-MB-231 through G0/G1 phase cell-cycle arrest

2018 ◽  
Vol Volume 11 ◽  
pp. 2409-2417 ◽  
Author(s):  
Longfei Yang ◽  
Huanran Liu ◽  
Min Long ◽  
Xi Wang ◽  
Fang Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Phase Cell ◽  
G1 Phase ◽  
Breast Cancer Cell Lines ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

2021 ◽  
Author(s):  
ulviye acar çevik ◽  
Ismail Celik ◽  
Ayşen IŞIK ◽  
Yusuf Özkay ◽  
Zafer Asım Kaplancıklı
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Evaluation Studies ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Anticancer Activities ◽  
Mcf 7

Abstract In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.

Novel Pyrazolyl Benzoxazole Conjugates: Design, Synthesis, Molecular Docking Studies and in vitro Anticancer Activities

2019 ◽  
Vol 16 (8) ◽  
pp. 619-626
Author(s):  
Arunkumar Thiriveedhi ◽  
Ratnakaram Venkata Nadh ◽  
Navuluri Srinivasu ◽  
Narayana Murthy Ganta
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Docking Studies ◽  
Anticancer Activities ◽  
Molecular Docking Studies ◽  
Hybrid Molecules ◽  
Mcf 7

Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values of <0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI50 of 0.34 µM. The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at the position of benzofuran of reference compound (N-acetyl pyrazoline derivative) might be valid for contributing to anti-cancer activity.

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.

The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1537-1537 ◽  
Author(s):  
C. Kurkjian ◽  
N. B. Janakiram ◽  
S. Guruswamy ◽  
C. V. Rao ◽  
H. Ozer
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Combination Therapy ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Low Dose ◽  
G1 Phase ◽  
Cycle Arrest ◽  
Dose Combination ◽  
Mcf 7

1537 Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p<0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p <0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer. No significant financial relationships to disclose.

scholarly journals Berberine Induces Apoptosis and Arrests Cell Cycle in Multiple Cancer Cell lines

2021 ◽  
Author(s):  
Qian Li ◽  
Hui Zhao ◽  
Weimin Chen ◽  
Ping Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
Multiple Cancer ◽  
Cycle Arrest ◽  
Ic50 Values ◽  
Mcf 7

IntroductionTo examine the anti-cancer effects of berberine on multiple cancer cell lines; and to clarify the underlying molecular mechanisms.Material and methodsThe IC50 values of berberine on Tca8113 (oral squamous cell carcinoma), CNE2 (nasopharyngeal carcinoma cell), MCF-7 (breast cancer), Hela (cervical carcinoma), and HT29 (colon cancer) cells were determined by MTT cell viability assay. Early apoptosis and cell cycle arrest was examined by flow cytometry with annexin V and propidium iodide (PI) staining, respectively. For expressions of BAX and BCL-2 genes and proteins were detected by real-time PCR and western blotting, respectively.ResultsBerberine displayed cytotoxic effect on all the cell lines tested. The IC50 values were determined (Tca8113, 218.52±18.71; CNE2, 249.18±18.14; MCF-7, 272.15±11.06; Hela, 245.18±17.33; and HT29, 52.37±3.45). PI staining revealed berberine treatment resulted in cell cycle arrest at G2/M. The treatment also induced early apoptosis as shown by annexin V staining. In addition, berberine significant elevated gene and protein expression of BAX, which was accompanied by substantial decreases in BCL-2 gene and protein levels. The effects of berberine on BAX and BCL-2 were time-dependent.ConclusionsBerberine exhibited cytotoxic effects on multiple cancer cell lines by inducing apoptosis and cell cycle arrest. The BCL-2/BAX signaling pathway may be the common pathway underlying the anti-tumor effect of berberine. The findings support the notion that berberine is a dietary compound that can be further developed into a drug candidate for cancer treatment.

Immobilization platform to induce quiescence in dormancy-capable cancer cells

TECHNOLOGY ◽  
2017 ◽  
Vol 05 (03) ◽  
pp. 129-138 ◽  
Author(s):  
Julian Adolfo Preciado ◽  
Eduardo Reátegui ◽  
Samira M. Azarin ◽  
Emil Lou ◽  
Alptekin Aksan
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Quiescent State ◽  
Cancer Relapse ◽  
Cycle Arrest ◽  
Mcf 7

Cancer dormancy emerges when tumor cells cease to proliferate but remain alive in a quiescent state. Recent evidence suggests that cancer cells can stay dormant in a patient’s body for years before returning to a proliferative state, leading to cancer relapse. The lack of a system to efficiently identify and study dormant cancer cells is currently limiting further diagnostic and treatment developments to prevent cancer relapse. Herein, we present a novel encapsulation platform to identify and study dormancy-capable cancer cells in a quiescent state by inhibiting proliferation through physical confinement. The platform involves the encapsulation of cells within a stiff silica-PEG hydrogel produced by a sol–gel technique. Cells are immobilized in a nondegradable microenvironment where proliferation and movement are inhibited due to physical confinement of the gel. The platform was tested using non-cancerous cell lines HFF, HUVEC, Jurkat, MEF, and MCF-10A, and cancer cell lines LnCAP, MCF-7, MCF10DCIS.com , MDA-MB-468, and OVCAR-5. Viability and metabolic activity measurements showed that MCF-7, LnCAP, and MCF10DCIS.COM cells remained metabolically active for up to 3 weeks while non-cancerous lines and the rest of the cancer cell lines did not survive after a few days. Ki-67 immunofluorescent staining confirmed that surviving MCF-7 cells underwent cell cycle arrest as early as 48 hours after encapsulation. Furthermore, following extraction and recovery, these cells resumed proliferation, indicating that the induced cell cycle arrest was reversible. These results conclude that physically inhibiting proliferation via the silica-PEG hydrogel system can be used to identify cells that can enter a quiescent state, setting the groundwork for this platform to be explored as a cancer cell dormancy model.

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