Cell cycle kinetics and the induction of programmed cell death by cytotoxic agents in tumour cells

AbstractAs like in mammalian system, the DNA damage responsive cell cycle checkpoint functions play crucial role for maintenance of genome stability in plants through repairing of damages in DNA and induction of programmed cell death or endoreduplication by extensive regulation of progression of cell cycle. ATM and ATR (ATAXIA-TELANGIECTASIA-MUTATED and -RAD3-RELATED) function as sensor kinases and play key role in the transmission of DNA damage signals to the downstream components of cell cycle regulatory network. The plant-specific NAC domain family transcription factor SOG1 (SUPPRESSOR OF GAMMA RESPONSE 1) plays crucial role in transducing signals from both ATM and ATR in presence of double strand breaks (DSBs) in the genome and found to play crucial role in the regulation of key genes involved in cell cycle progression, DNA damage repair, endoreduplication and programmed cell death. Here we report that Arabidopsis exposed to high salinity shows generation of oxidative stress induced DSBs along with the concomitant induction of endoreduplication, displaying increased cell size and DNA ploidy level without any change in chromosome number. These responses were significantly prominent in SOG1 overexpression line than wild-type Arabidopsis, while sog1 mutant lines showed much compromised induction of endoreduplication under salinity stress. We have found that both ATM-SOG1 and ATR-SOG1 pathways are involved in the salinity mediated induction of endoreduplication. SOG1was found to promote G2-M phase arrest in Arabidopsis under salinity stress by downregulating the expression of the key cell cycle regulators, including CDKB1;1, CDKB2;1, and CYCB1;1, while upregulating the expression of WEE1 kinase, CCS52A and E2Fa, which act as important regulators for induction of endoreduplication. Our results suggest that Arabidopsis undergoes endoreduplicative cycle in response to salinity induced DSBs, showcasing an adaptive response in plants under salinity stress.

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Mk 886 Functions As A Radiomimetic Agent: Genomic Responses Related to Oxidative Stress, The Cell Cycle, Proliferation and Programmed Cell Death in Panc-1 Cells

Advances in Experimental Medicine and Biology - Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5 ◽

10.1007/978-1-4615-0193-0_70 ◽

2002 ◽

pp. 451-456 ◽

Cited By ~ 2

Author(s):

Ken M. Anderson ◽

Waddah Alrefai ◽

Colin Anderson ◽

Philip Bonomi ◽

Jules Harris

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Cell Death ◽

Programmed Cell Death

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Differentiating life and death: An inflammatory affair

10.7287/peerj.preprints.27080v1 ◽

2018 ◽

Author(s):

Dustin Lane

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Death ◽

Cell Differentiation ◽

Programmed Cell Death ◽

Signaling Networks ◽

Inhibitors Of Apoptosis ◽

Life And Death ◽

Cell Death Signaling ◽

Cycle Dependent

Programmed cell death signaling networks are frequently activated to coordinate the process of cell differentiation, and a variety of apoptotic events can mediate the process. This can include the ligation of death receptors, the activation of downstream caspases, and the induction of chromatin fragmentation, and all of these events can occur without downstream induction of death. Importantly, regulators of programmed cell death also have established roles in mediating differentiation. This review will provide an overview of apoptosis and its regulation by Inhibitors of Apoptosis (IAPs) and Bcl-2 family members. It will then outline the cross-talk between NF-ĸB and apoptotic signaling in the regulation of apoptosis before discussing the function of these regulators in the control of cell differentiation. It will end on a discussion of how a DNA damage-directed, cell cycle-dependent differentiation program may be controlled across multiple passages through cell cycle, and will assert that the failure to properly differentiate is the underlying cause of cancer.

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Juggling Surface Charges of 2D Niobium Carbide MXenes for a Reactive Oxygen Species Scavenging and Effective Targeting of the Malignant Melanoma Cell Cycle into Programmed Cell Death

ACS Sustainable Chemistry & Engineering ◽

10.1021/acssuschemeng.0c01609 ◽

2020 ◽

Vol 8 (21) ◽

pp. 7942-7951 ◽

Cited By ~ 3

Author(s):

Agnieszka Jastrzebska ◽

Aleksandra Szuplewska ◽

Anita Rozmysłowska-Wojciechowska ◽

Joanna Mitrzak ◽

Tomasz Wojciechowski ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Cycle ◽

Cell Death ◽

Malignant Melanoma ◽

Programmed Cell Death ◽

Melanoma Cell ◽

Niobium Carbide ◽

Oxygen Species ◽

Surface Charges ◽

Malignant Melanoma Cell

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Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.11.3674 ◽

1998 ◽

Vol 16 (11) ◽

pp. 3674-3690 ◽

Cited By ~ 145

Author(s):

D M Bradshaw ◽

R J Arceci

Keyword(s):

Drug Resistance ◽

Cell Death ◽

Multidrug Resistance ◽

Programmed Cell Death ◽

Tumor Cells ◽

Efflux Pump ◽

Active Form ◽

Cytotoxic Agents ◽

Transport Systems ◽

Drug Efflux

For cytotoxic agents to have an effect on tumor cells, drugs must first be transported into the cell, potentially be metabolized to an active form, and interact appropriately with target molecules. A final common pathway of cytotoxic agents is usually the initiation of programmed cell death, or apoptosis. Tumor cells overcome the effects of cytotoxic agents at one or more of these levels. The classic multidrug-resistance (MDR) phenotype, as mediated by the drug efflux pump, P-glycoprotein, is one of the most extensively studied mechanisms of drug resistance. Additional drug transporters, such as the multidrug resistance-associated proteins (MRPs), have also been identified and can convey drug-resistance phenotypes. Important questions remain as to how and whether such transport systems can be specifically measured and effectively targeted to improve therapeutic outcomes. Furthermore, alterations in drug targets, drug metabolism, repair of DNA damage caused by drugs, and the inability to initiate programmed cell death can all contribute to drug resistance and must be ultimately considered in the explanation of tumor-cell resistance to therapy. Continued exploration of the pharmacologic methods to circumvent drug resistance, as well as strategies that involve targeted therapy and immunomodulation, should increase the specificity and efficacy of treatments for patients with cancer.

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Measurement of cell-cycle phase-specific cell death using Hoechst 33342 and propidium iodide: preservation by ethanol fixation.

Journal of Histochemistry & Cytochemistry ◽

10.1177/36.9.2457047 ◽

1988 ◽

Vol 36 (9) ◽

pp. 1147-1152 ◽

Cited By ~ 34

Author(s):

G Ciancio ◽

A Pollack ◽

M A Taupier ◽

N L Block ◽

G L Irvin

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Propidium Iodide ◽

Cell Cycle Phase ◽

Cytotoxic Agents ◽

Cycle Phase ◽

Specific Cell ◽

Dead Cell ◽

Hoechst 33342 ◽

The Dead

We developed a rapid technique for preservation of Hoechst 33342/propidium iodide-stained cells, using ethanol as a fixative. Combined staining with these dyes makes possible analysis of cell-cycle phase-specific cell death. The technique relies on exclusion of propidium iodide from the viable cells, whereas Hoechst stains all of the cells. The bivariate histograms resulting from the flow cytometric analysis contain the equivalent of two single-parameter DNA histograms, one of the living and the other of the dead cell population. Preservation of staining involved addition of 25% ethanol in PBS after propidium iodide staining and before Hoechst staining. The separation between the living and the dead cell populations was maintained for over 3 days at 4 degrees C. This technique will be valuable for quantitative evaluation of the cell-cycle phase-specific effects of cytostatic or cytotoxic agents, particularly in situations where a lag period between staining and analysis is unavoidable.

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