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.

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.

scholarly journals CCT Chaperonin Complex Is Required for the Biogenesis of Functional Plk1

2005 ◽  
Vol 25 (12) ◽  
pp. 4993-5010 ◽  
Author(s):  
Xiaoqi Liu ◽  
Chin-Yo Lin ◽  
Ming Lei ◽  
Shi Yan ◽  
Tianhua Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Mammalian Cells ◽  
Active Form ◽  
Cycle Arrest ◽  
Cdc2 Activity ◽  
Partial Depletion

ABSTRACT Experiments from several different organisms have demonstrated that polo-like kinases are involved in many aspects of mitosis and cytokinesis. Here, we provide evidence to show that Plk1 associates with chaperonin-containing TCP1 complex (CCT) both in vitro and in vivo. Silencing of CCT by use of RNA interference (RNAi) in mammalian cells inhibits cell proliferation, decreases cell viability, causes cell cycle arrest with 4N DNA content, and leads to apoptosis. Depletion of CCT in well-synchronized HeLa cells causes cell cycle arrest at G2, as demonstrated by a low mitotic index and Cdc2 activity. Complete depletion of Plk1 in well-synchronized cells also leads to G2 block, suggesting that misfolded Plk1 might be responsible for the failure of CCT-depleted cells to enter mitosis. Moreover, partial depletion of CCT or Plk1 leads to mitotic arrest. Finally, the CCT-depleted cells reenter the cell cycle upon reintroduction of the purified constitutively active form of Plk1, indicating that Plk1 might be a CCT substrate.

scholarly journals An In Vitro Anticancer Activity Evaluation of Neolamarckia cadamba (Roxb.) Bosser Leaves’ Extract and its Metabolite Profile

2021 ◽  
Vol 12 ◽  
Author(s):  
Shakirah Razali ◽  
Al’aina Yuhainis Firus Khan ◽  
Alfi Khatib ◽  
Qamar Uddin Ahmed ◽  
Ridhwan Abdul Wahab ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Ethanol Extract ◽  
Anticancer Effect ◽  
Chromatography Analysis ◽  
Cycle Arrest ◽  
Mcf 7

The leaves of Neolamarckia cadamba (NC) (Roxb.) Bosser (family: Rubiaceae) are traditionally used to treat breast cancer in Malaysia; however, this traditional claim is yet to be scientifically verified. Hence, this study was aimed to evaluate the anticancer effect of NC leaves’ ethanol extract against breast cancer cell line (MCF-7 cells) using an in vitro cell viability, cytotoxicity, and gene expression assays followed by the gas chromatography analysis to further confirm active principles. Results revealed 0.2 mg/ml as the half maximal inhibitory concentration (IC50) against MCF-7. The extract exerted anticancer effect against MCF-7 cells in a dose- and time-dependent manner. The cell cycle assay showed that the extract arrested MCF-7 cells in the G0/G1 phase, and apoptosis was observed after 72 h by the Annexin-V assay. The gene expression assay revealed that the cell cycle arrest was associated with the downregulation of CDK2 and subsequent upregulation of p21 and cyclin E. The extract induced apoptosis via the mediation of the mitochondrial cell death pathways. A chromatography analysis revealed the contribution of D-pinitol and myo-inositol as the two major bioactive compounds to the activity observed. Overall, the study demonstrated that NC leaves’ ethanol extract exerts anticancer effect against MCF-7 human breast cancer cells through the induction of apoptosis and cell cycle arrest, thereby justifying its traditional use for the treatment of breast cancer in Malaysia.

scholarly journals A Marine Alkaloid, Ascomylactam A, Suppresses Lung Tumorigenesis via Inducing Cell Cycle G1/S Arrest through ROS/Akt/Rb Pathway

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 494
Author(s):  
Lan Wang ◽  
Yun Huang ◽  
Cui-hong Huang ◽  
Jian-chen Yu ◽  
Ying-chun Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Molecular Mechanisms ◽  
Soft Agar ◽  
Ros Generation ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest

Ascomylactam A was reported for the first time as a new 13-membered-ring macrocyclic alkaloid in 2019 from the mangrove endophytic fungus Didymella sp. CYSK-4 from the South China Sea. The aim of our study was to delineate the effects of ascomylactam A (AsA) on lung cancer cells and explore the antitumor molecular mechanisms underlying of AsA. In vitro, AsA markedly inhibited the cell proliferation with half-maximal inhibitory concentration (IC50) values from 4 to 8 μM on six lung cancer cell lines, respectively. In vivo, AsA suppressed the tumor growth of A549, NCI-H460 and NCI-H1975 xenografts significantly in mice. Furthermore, by analyses of the soft agar colony formation, 5-ethynyl-20-deoxyuridine (EdU) assay, reactive oxygen species (ROS) imaging, flow cytometry and Western blotting, AsA demonstrated the ability to induce cell cycle arrest in G1 and G1/S phases by increasing ROS generation and decreasing of Akt activity. Conversely, ROS inhibitors and overexpression of Akt could decrease cell growth inhibition and cell cycle arrest induced by AsA. Therefore, we believe that AsA blocks the cell cycle via an ROS-dependent Akt/Cyclin D1/Rb signaling pathway, which consequently leads to the observed antitumor effect both in vitro and in vivo. Our results suggest a novel leading compound for antitumor drug development.

scholarly journals Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 396 ◽  
Author(s):  
Lukasz Skalniak ◽  
Justyna Kocik ◽  
Justyna Polak ◽  
Anna Skalniak ◽  
Monika Rak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Clinical Trials ◽  
Cell Cycle Arrest ◽  
De Novo ◽  
Phase Iii ◽  
Prolonged Treatment ◽  
Secondary Resistance ◽  
Cycle Arrest ◽  
Mcf 7

The protein p53 protects the organism against carcinogenic events by the induction of cell cycle arrest and DNA repair program upon DNA damage. Virtually all cancers inactivate p53 either by mutations/deletions of the TP53 gene or by boosting negative regulation of p53 activity. The overexpression of MDM2 protein is one of the most common mechanisms utilized by p53wt cancers to keep p53 inactive. Inhibition of MDM2 action by its antagonists has proved its anticancer potential in vitro and is now tested in clinical trials. However, the prolonged treatment of p53wt cells with MDM2 antagonists leads to the development of secondary resistance, as shown first for Nutlin-3a, and later for three other small molecules. In the present study, we show that secondary resistance occurs also after treatment of p53wt cells with idasanutlin (RG7388, RO5503781), which is the only MDM2 antagonist that has passed phase II and entered phase III clinical trials, so far. Idasanutlin strongly activates p53, as evidenced by the induction of p21 expression and potent cell cycle arrest in all the three cell lines tested, i.e., MCF-7, U-2 OS, and SJSA-1. Notably, apoptosis was induced only in SJSA-1 cells, while MCF-7 and U-2 OS cells were able to restore the proliferation upon the removal of idasanutlin. Moreover, idasanutlin-treated U-2 OS cells could be cultured for long time periods in the presence of the drug. This prolonged treatment led to the generation of p53-mutated resistant cell populations. This resistance was generated de novo, as evidenced by the utilization of monoclonal U-2 OS subpopulations. Thus, although idasanutlin presents much improved activities compared to its precursor, it displays the similar weaknesses, which are limited elimination of cancer cells and the generation of p53-mutated drug-resistant subpopulations.

scholarly journals Evaluation of Anticancer Activity of Neolamarckia Cadamba Leaves and Its Metabolite Profile

2021 ◽  
Author(s):  
Shakirah Razali ◽  
Al’aina Firus Khan ◽  
Alfi Khatib ◽  
Qamar Uddin Ahmed ◽  
Habibah Hassan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Traditional Use ◽  
Chromatography Analysis ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Abstract Neolamarckia cadamba (NC) leaf is traditionally used for the treatment of breast cancer, however this claim is unverified. This study aimed to evaluate the anti-cancer activities of NC leaf ethanol extract on breast cancer cell line (MCF-7 cells) using in vitro cell viability, cytotoxicity and gene expression assays followed by gas chromatography analysis. Results revealed inhibition concentration (IC50) against MCF-7 at 0.2 mg/mL. The extract exerted a dose and time dependent inhibitory effect against MCF-7 cells. The cell cycle assay showed that the extract arrested MCF-7 cells in G0/G1 phase, and apoptosis were observed after 72 hours by Annexin-V assay. The gene expression assay revealed that the cell cycle arrest was associated with the down-regulation of CDK2 and subsequent up-regulation of p21 and cyclin E. The extract induced apoptosis via mediation of the mitochondrial cell death pathways. Chromatography analysis revealed the contribution of d-pinitol and myo-inositol to the activity observed as the two major bioactive compounds. Overall, the study demonstrated that NC exerts anti-cancer effect on MCF-7 human breast cancer cells through induction of apoptosis and cell cycle arrest thus justifying its traditional use for breast cancer treatment in Malaysia.

Cytotoxic and cell cycle arrest induction of pentacyclic triterpenoides separated from Lantana camara leaves against MCF-7 cell line in vitro

2018 ◽  
Vol 46 (1) ◽  
pp. 381-390 ◽  
Author(s):  
Zahraa R. Shamsee ◽  
Ali Z. Al-Saffar ◽  
Ahmed F. Al-Shanon ◽  
Jameel R. Al-Obaidi
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Lantana Camara ◽  
Cycle Arrest ◽  
Mcf 7

Foeniculum Vulgare and Pelargonium Graveolens Essential Oil Mixture Triggers the Cell Cycle Arrest and Apoptosis in MCF-7 Cells

2019 ◽  
Vol 19 (9) ◽  
pp. 1103-1113 ◽  
Author(s):  
Islam El-Garawani ◽  
Sobhy Hassab El Nabi ◽  
Ebtesam Nafie ◽  
Samar Almeldin
Keyword(s):  
Cell Cycle ◽  
Essential Oil ◽  
Cell Cycle Arrest ◽  
Cell Cycle Distribution ◽  
Distribution Analysis ◽  
Foeniculum Vulgare ◽  
Anticancer Properties ◽  
Cycle Arrest ◽  
Mcf 7

Background: Fennel (Foeniculum vulgare) and rose geranium (Pelargonium graveolens) oils are known for their various biological effects including anticancer properties. Objective: This study aimed to evaluate the anticancer mechanism of fennel and geranium oils combined treatment on MCF-7 cells. Methods: The GC-MS method for essential oil characterization as well as the in vitro cytotoxicity, morphological changes, real-time PCR and immunocytochemical investigation for apoptosis-related markers, in addition, to flow cytometric cell cycle distribution analysis were done. Results: The major constituents of both essential oils were anethole (55.33 %) and estragole (11.57 %) for fennel essential oil. However, cintronellol (34.40 %) and geraniol (8.67 %) were identified in geranium oil. The results revealed an IC50 of 220±5.7 and 60±2.1µg/ml for fennel and geranium oils, respectively. The mechanistic anticancer properties were investigated throughout the 70, 50, and 25µg/ml of oils mixture. The marked apoptotic morphology and the flow cytometric cell cycle distribution analysis in addition to the levels of apoptosisrelated makers such as p53, caspase-3, mir-21, mir-92a, Bcl-2, and ki-67 confirmed that fennel and geranium oils combination induced cell cycle arrest and apoptosis in MCF-7 cells. Moreover, the oils mixture did not exert any significant (P<0.01) toxicity on normal human peripheral blood lymphocytes in vitro. Conclusion: The findings showed that the mixture of oils exerted selective cytotoxicity towards MCF-7 cells through induction of cell cycle arrest and apoptosis which may be triggered by the synergistic effect between the active ingredients of fennel and geranium oils.

scholarly journals Persea declinata(Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells viaG0/G1Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Putri Narrima ◽  
Mohammadjavad Paydar ◽  
Chung Yeng Looi ◽  
Yi Li Wong ◽  
Hairin Taha ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Crude Extract ◽  
Persea Americana ◽  
Cell Permeability ◽  
Ros Generation ◽  
Dependent Manner ◽  
Anticancer Properties ◽  
Cycle Arrest ◽  
Mcf 7

Persea declinata(Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americanaMill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties ofPersea declinata(Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

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