Luteoloside Inhibits Proliferation of Human Chronic Myeloid Leukemia K562 Cells by Inducing G2/M Phase Cell Cycle Arrest and Apoptosis

Chronic myeloid leukemia (CML) is a malignant tumor caused by the abnormal proliferation of hematopoietic stem cells. Among a new series of acridone derivatives previously synthesized, it was found that the methoxybenzyl 5-nitroacridone derivative 8q has nanomolar cytotoxicity in vitro against human chronic myelogenous leukemia K562 cells. In order to further explore the possible anti-leukemia mechanism of action of 8q on K562 cells, a metabolomics and molecular biology study was introduced. It was thus found that most of the metabolic pathways of the G1 phase of K562 cells were affected after 8q treatment. In addition, a concentration-dependent accumulation of cells in the G1 phase was observed by cell cycle analysis. Western blot analysis showed that 8q significantly down-regulated the phosphorylation level of retinoblastoma-associated protein (Rb) in a concentration-dependent manner, upon 48 h treatment. In addition, 8q induced K562 cells apoptosis, through both mitochondria-mediated and exogenous apoptotic pathways. Taken together, these results indicate that 8q effectively triggers G1 cell cycle arrest and induces cell apoptosis in K562 cells, by inhibiting the CDK4/6-mediated phosphorylation of Rb. Furthermore, the possible binding interactions between 8q and CDK4/6 protein were clarified by homology modeling and molecular docking. In order to verify the inhibitory activity of 8q against other chronic myeloid leukemia cells, KCL-22 cells and K562 adriamycin-resistant cells (K562/ADR) were selected for the MTT assay. It is worth noting that 8q showed significant anti-proliferative activity against these cell lines after 48 h/72 h treatment. Therefore, this study provides new mechanistic information and guidance for the development of new acridones for application in the treatment of CML.

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A Novel DNA Topoisomerase I Inhibitor with Different Mechanism from Camptothecin Induces G2/M Phase Cell Cycle Arrest to K562 Cells

Biochemistry ◽

10.1021/bi1009419 ◽

2010 ◽

Vol 49 (47) ◽

pp. 10131-10136 ◽

Cited By ~ 39

Author(s):

Ning Wu ◽

Xi-Wei Wu ◽

Keli Agama ◽

Yves Pommier ◽

Jun Du ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Topoisomerase I ◽

K562 Cells ◽

Phase Cell ◽

Dna Topoisomerase I ◽

Dna Topoisomerase ◽

Topoisomerase I Inhibitor ◽

Cycle Arrest ◽

M Phase

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The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

Molecules ◽

10.3390/molecules25030501 ◽

2020 ◽

Vol 25 (3) ◽

pp. 501

Author(s):

So Hyun Park ◽

Ji-Young Hong ◽

Hyen Joo Park ◽

Sang Kook Lee

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Antiproliferative Activity ◽

Hepatoma Cells ◽

Phase Cell ◽

Human Hepatoma Cells ◽

Cycle Arrest ◽

Growth Inhibitory Activity ◽

M Phase

Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.

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N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamides Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

New Journal of Chemistry ◽

10.1039/d1nj02550c ◽

2022 ◽

Author(s):

Selvaraj Shyamsivappan ◽

Raju Vivek ◽

Thangaraj Suresh ◽

Palanivel Naveen ◽

Kaviyarasu Adhigaman ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Spectroscopic Studies ◽

Phase Cell ◽

X Ray ◽

Cycle Arrest ◽

M Phase ◽

Mcf 7

A progression of new N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamide derivatives were synthesized from potent 8-nitro quinoline-thiosemicarbazones. The synthesized compounds were characterized by different spectroscopic studies and single X-ray crystallographic studies. The compounds were...

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

10.21203/rs.3.rs-289802/v1 ◽

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.

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