Ciprofloxacin-mediated induction of S-phase cell cycle arrest and apoptosis in COLO829 melanoma cells

Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.

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Legionella pneumophila translocated translation inhibitors are required for bacterial-induced host cell cycle arrest

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1820093116 ◽

2019 ◽

Vol 116 (8) ◽

pp. 3221-3228 ◽

Cited By ~ 6

Author(s):

Asaf Sol ◽

Erion Lipo ◽

Dennise A. de Jesús-Díaz ◽

Connor Murphy ◽

Mildred Devereux ◽

...

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Cell Cycle Arrest ◽

Host Cell ◽

Legionella Pneumophila ◽

S Phase ◽

Phase Cell ◽

Cycle Arrest ◽

Bacterial Replication ◽

Cell Cycle Machinery

The cell cycle machinery controls diverse cellular pathways and is tightly regulated. Misregulation of cell division plays a central role in the pathogenesis of many disease processes. Various microbial pathogens interfere with the cell cycle machinery to promote host cell colonization. Although cell cycle modulation is a common theme among pathogens, the role this interference plays in promoting diseases is unclear. Previously, we demonstrated that the G1 and G2/M phases of the host cell cycle are permissive for Legionella pneumophila replication, whereas S phase provides a toxic environment for bacterial replication. In this study, we show that L. pneumophila avoids host S phase by blocking host DNA synthesis and preventing cell cycle progression into S phase. Cell cycle arrest upon Legionella contact is dependent on the Icm/Dot secretion system. In particular, we found that cell cycle arrest is dependent on the intact enzymatic activity of translocated substrates that inhibits host translation. Moreover, we show that, early in infection, the presence of these translation inhibitors is crucial to induce the degradation of the master regulator cyclin D1. Our results demonstrate that the bacterial effectors that inhibit translation are associated with preventing entry of host cells into a phase associated with restriction of L. pneumophila. Furthermore, control of cyclin D1 may be a common strategy used by intracellular pathogens to manipulate the host cell cycle and promote bacterial replication.

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Paris Saponin VII Induces Apoptosis and Cell Cycle Arrest in Erythroleukemia Cells by a Mitochondrial Membrane Signaling Pathway

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200615134039 ◽

2020 ◽

Vol 20 ◽

Author(s):

Xin Lin ◽

Babu Gajendran ◽

Krishnapriya M. Varier ◽

Wuling Liu ◽

Jingrui Song ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Mtt Assay ◽

Mitochondrial Membrane ◽

Antimicrobial Activities ◽

Mitochondrial Pathway ◽

S Phase ◽

Phase Cell ◽

Cycle Arrest ◽

Hel Cells

Background and Purpose: Leukemia considered a top-listed ailment, according to WHO, which contributes to the death of a major population of the world every year. Paris Saponin VII (PS), a saponin which was isolated from the roots of Trillium kamtschaticum, from our group, was reported to provide hemostatic, cytotoxic and antimicrobial activities. However, its molecular mechanism underlying the anti-proliferative effects remains unclear. Thus, this study hypothesized to assess that mechanism in PS treated HEL cells. Methods: The MTT assay used to analyze the PS inhibited cell viability in the HEL cells. We further found that PS could induce S phase cell cycle arrest through flow cytometry as well as the western blot analysis of intrinsic and extrinsic apoptotic molecules. Results: The MTT assay showed the IC50 concentration of PS as 0.667μM. The study revealed that PS treatment inhibits cell proliferation dose-dependently. It further caused mitochondrial membrane potential changes by PS treatment. Mechanistic protein expression revealed a dose-dependent upsurge for Bid and Bim molecules, while Bcl2 and PARP expression levels were significantly (P< 0.05) down-regulated in PS treated HEL cells resulting in caspase -3 release and increased the Bim levels upon 24h of incubation. Conclusions: These findings indicate that PS possesses an excellent anti-leukemic activity via regulation of the mitochondrial pathway, leading to S phase cell cycle arrest and caspase-dependent apoptosis suggesting it as a potential alternative chemotherapeutic agent for leukemia patients.

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