scholarly journals Synthesis and In Vitro Antitumor Activity of Naringenin Oxime and Oxime Ether Derivatives

2019 ◽  
Vol 20 (9) ◽  
pp. 2184 ◽  
Author(s):  
Ahmed Dhahir Latif ◽  
Tímea Gonda ◽  
Máté Vágvölgyi ◽  
Norbert Kúsz ◽  
Ágnes Kulmány ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Gynecological Cancer ◽  
Human Leukemia ◽  
Oxime Ether ◽  
M Phase ◽  
Induced Apoptosis ◽  
Mcf 7

Naringenin is one of the most abundant dietary flavonoids exerting several beneficial biological activities. Synthetic modification of naringenin is of continuous interest. During this study our aim was to synthesize a compound library of oxime and oxime ether derivatives of naringenin, and to investigate their biological activities. Two oximes and five oxime ether derivatives were prepared; their structure has been elucidated by NMR and high-resolution mass spectroscopy. The antiproliferative activity of the prepared compounds was evaluated by MTT assay against human leukemia (HL-60) and gynecological cancer cell lines isolated from cervical (HeLa, Siha) and breast (MCF-7, MDA-MB-231) cancers. Tert-butyl oxime ether derivative exerted the most potent cell growth inhibitory activity. Moreover, cell cycle analysis suggested that this derivative caused a significant increase in the hypodiploid (subG1) phase and induced apoptosis in Hela and Siha cells, and induced cell cycle arrest at G2/M phase in MCF-7 cells. The proapoptotic potential of the selected compound was confirmed by the activation of caspase-3. Antioxidant activities of the prepared molecules were also evaluated with xanthine oxidase, DPPH and ORAC assays, and the methyl substituted oxime ether exerted the most promising activity.

scholarly journals 3,3′-Diindolylmethane: A Promising Sensitizer ofγ-Irradiation

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Wenjing Wang ◽  
Maomin Lv ◽  
Chaoji Huangfu ◽  
Fang Wang ◽  
Jingang Zhang
Keyword(s):  
Cell Cycle ◽  
Phase Cell ◽  
Cell Cycle Distribution ◽  
Effective Treatment Modality ◽  
Intracellular Ros ◽  
M Phase ◽  
Induced Apoptosis ◽  
Mtt Assays ◽  
Mcf 7

Purpose. Radiotherapy is an effective treatment modality in the clinical treatment of breast cancer. The present work investigated the effect of 3,3′-diindolylmethane (DIM) onγ-irradiation sensitizing human breast carcinoma.Methods. Cell survival, intracellular ROS levels, cell cycle distribution, cell apoptosis, and expression of proteins related to apoptosis were measured with MTT assays, flow cytometry, and Western blot analysis, respectively.Results.In vitroDIM plusγ-irradiation arrested the activity of G2/M phase cell cycle, increased intracellular ROS level, significantly suppressed PARP (poly ADP-ribose polymerase), and enhancedγ-irradiation-induced apoptosis, thereby inhibiting the proliferation of MCF-7 cells.Conclusion. These data provide a rationale for the use of DIM as a promising sensitizer ofγ-irradiation.

Novel Thiadiazoline Spiro Quinoline Analogues Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

2021 ◽  
Author(s):  
Selvaraj Shyamsivappan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Adhigaman Kaviyarasu ◽  
Sundarasamy Amsaveni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Spectroscopic Studies ◽  
Phase Cell ◽  
Quinoline Derivatives ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

Abstract A progression of novel thiadiazoline spiro quinoline derivatives were synthesized from potent thiadiazoline spiro quinoline derivatives . The synthesized compounds portrayed by different spectroscopic studies and single X-ray crystallographic studies. The compounds were assessed for in vitro anticancer properties towards MCF-7 and HeLa cells. The compounds showed superior inhibition action MCF-7 malignant growth cells. Amongst, the compound 4a showed significant inhibition activity, the cell death mechanism was evaluated by fluorescent staining, and flow cytometry, RT-PCR, and western blot analyses. The in vitro anticancer results revealed that the compound 4a induced apoptosis by inhibition of estrogen receptor alpha (ERα) and G2/M phase cell cycle arrest. The binding affinity of the compounds with ERα and pharmacokinetic properties were confirmed by molecular docking studies.

In vitro Cytotoxicity, Apoptosis, Effects on Cell Cycle Kinetics and Schedule-Dependent Effects Induced by Paclitaxel on C6 and CHO-K1 Cell Lines

2020 ◽  
Author(s):  
Mohammad Aamir Bhat ◽  
Chandresh Varshneya ◽  
Pallavi Bhardwaj ◽  
Rajendra Damu Patel ◽  
Ashok Kumar Panda
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Prolonged Exposure ◽  
Fluorescent Microscopy ◽  
In Vitro Cytotoxicity ◽  
M Phase ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
In Vitro Data

Exposure of C6 and CHO-K1 cells to different concentrations of the antineoplastic drug paclitaxel resulted in a loss of cellular viability. The percentage of surviving cells fell significantly after 48 hours of treatment and IC50 values observed were between 0.5 to 0.75 and 0.25 to 0.75 µg/ml in C6 and CHO-K1 cells, respectively. No significant cytotoxicity was observed after 24 hours of treatment and cells incubated at higher concentrations of paclitaxel showed increased survivability. Paclitaxel induced apoptosis by caspase 3/7 activation and caused accumulation of cells in the G2/M phase of the cell cycle. Upon fluorescent microscopy, both the cell lines lost the morphology, confluence and adherence at 24 hours but effects were much more pronounced at 48 hours of treatment. The in vitro data suggested that paclitaxel is highly effective when there is prolonged exposure of tumor to the drug rather than increasing the intratumoral or biophasic concentration of the drug. 

scholarly journals Effect of Sterols Isolated fromMyrtillocactus geometrizanson Growth Inhibition of Colon and Breast Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Mario Augusto Bolaños-Carrillo ◽  
Jose Luis Ventura-Gallegos ◽  
Arturo David Saldivar-Jiménez ◽  
Alejandro Zentella-Dehesa ◽  
Mariano Martínez-Vázquez
Keyword(s):  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Biological Activities ◽  
Annexin V ◽  
Parp Cleavage ◽  
Dependent Manner ◽  
Cycle Dependent ◽  
Mcf 7

Objective. To explore the effect of peniocerol and macdougallin on HCT-15 and MCF-7 cells proliferation, cell cycle, apoptosis, and PARP cleavage.Methods. HCT-15 and MCF-7 cells were treated with various concentrations of peniocerol and macdougallin (10–80 μM) during 24 or 48 h. Crystal Violet Assay was used to evaluate the inhibition effect. Cell cycle regulation was examined by a propidium iodide method. Cell apoptosis was detected through both Annexin–V FLUOS/PI double-labeled cytometry assays and Western blot was applied to assess PARP cleavage.Results. Peniocerol and macdougallin induced growth inhibition and apoptosisin vitroin a time- and dose-dependent manner. Moreover, peniocerol and macdougallin induced arrest of cell cycle-dependent manner and increased the proportion of cells in G0/G1phase. PARP cleavage in HCT-15 and MCF-7 cells was induced by treatment with peniocerol and macdougallin after 36 hours.Conclusions. Our results showed that the mechanism of cytotoxicity displayed by peniocerol and macdougallin is related to cell cycle arrest and apoptosis in both cell lines. This is a significant observation because it helps to understand the way some oxysterols isolated fromMyrtillocactus geometrizansdevelop their biological activities against cancer cells.

Novel phenyl and thiophene dispiro indenoquinoxaline pyrrolidine quinolones induced apoptosis via G1/S and G2/M phase cell cycle arrest in MCF-7 cells

2020 ◽  
Vol 44 (35) ◽  
pp. 15031-15045
Author(s):  
Selvaraj Shyamsivappan ◽  
Arjunan Saravanan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Ramasamy Shankar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycloaddition Reaction ◽  
Phase Cell ◽  
One Pot ◽  
Cycle Arrest ◽  
M Phase ◽  
Induced Apoptosis ◽  
Mcf 7

New phenyl and thiophene dispiro indeno quinoxaline pyrrolidine quinolone analogues were synthesized by a one-pot four-component [3+2] cycloaddition reaction between (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones, o-phenylenediamine, ninhydrin, and benzylamine/thiophenemethylamine.

scholarly journals Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1073 ◽  
Author(s):  
Mina Ryu ◽  
Chung Ki Sung ◽  
Young Jun Im ◽  
ChangJu Chun
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Mammalian Cells ◽  
Biological Activities ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ros Generation ◽  
Cycle Arrest ◽  
Alnus Hirsuta ◽  
Mcf 7

JNK and p38 are important mitogen-activated protein kinases (MAPKs) that respond to stress stimuli. The stress-activated MAPKs associated with apoptotic cell death play vital roles in mammalian cells. Alnus hirsuta, which contains abundant diarylheptanoids derivatives, is a valuable medicinal plant. The CHCl3 extract (AHC) containing platyphyllenone (1) and platyphyllone (3) as main compounds showed in vitro anticancer effects. We report the biological activities of A. hirsuta extract associated with the regulation of apoptosis and JNK and p38 in MCF-7 breast cancer cells. Levels of phospho-JNK and phospho-p38 by AHC treatment were evaluated by enzyme-linked immunosorbent assay (ELISA). ROS production, apoptotic effect, and DNA contents of the cells were measured by flow cytometry. The two diarylheptanoids 1 and 3 and the AHC extract exhibited cytotoxic effects on MCF-7 cells in MTT assay, with IC50 values of 18.1, 46.9, 260.0 μg/mL, respectively. AHC induced ROS generation and elevated the endogenous levels of phospho-JNK and phospho-p38. AHC resulted in apoptosis and cell cycle arrest. We suggest that the antitumor effect of A. hirsuta extract is achieved by apoptosis promotion and cell cycle arrest mediated by the activation of JNK and p38 signaling pathway via ROS generation.

scholarly journals Investigating the in Vitro Antiproliferative and Apoptosis-Inducing Effects of Pyranochromene Derivatives

2020 ◽  
Vol 11 (3) ◽  
pp. 10987-10995
Keyword(s):  
Cell Lines ◽  
Biological Activities ◽  
Para Position ◽  
Lead Compounds ◽  
Three Component Reaction ◽  
Anti Cancer ◽  
Important Health ◽  
Induced Apoptosis ◽  
Mcf 7

Cancer is one of the important health problems, and researchers continue their efforts to discover new anti-cancer agents. Coumarins (chromene-2-ones), a group of natural metabolites, have shown different biological activities based on their substitutions. In this study, 15 compounds of 1,5-dihydropyrano[2,3-c]chromene were synthesized by three-component reaction and investigated for the antiproliferative activity on the breast (MCF-7), colorectal (SW48 and HT-29), lung (A549), and brain (U-87 MG) cancer cell lines as well as two normal cell lines (3T3 and HUVEC). The apoptosis/necrosis-inducing effect of the selected compounds was determined on the MCF-7 cell line by flow cytometry. The results showed that the compounds bearing a moiety on their phenyl ring's para position had potent cytotoxic effects on the tested cell lines. These compounds induced apoptosis in MCF-7 cells. The compounds were also toxic for 3T3 and HUVECs and did not display a high selectivity for tumor cells. Our results revealed that the compounds having a moiety at the para position of their phenyl ring might be suitable lead compounds for the synthesis of potent anti-cancer agents.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

2020 ◽  
Vol 16 (3) ◽  
pp. 340-349
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Ernest Hamel ◽  
Zahra Shahsavari ◽  
Mohsen Alipour ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Neuropathy ◽  
Cell Line ◽  
Normal Cell ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Cell Line ◽  
Anti Cancer ◽  
Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

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