Dinstinct ROS and biochemical profiles in cells undergoing DNA damage-induced senescence and apoptosis

Song, Yong Jin; Lee, Bo Yun; Hwang, Eun Seong

doi:10.1016/j.mad.2004.11.008

Cited by 79 publications

(59 citation statements)

References 46 publications

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“…29,30 However, it has also been reported that significant levels of ROS are produced in senescing cells, but not in apoptotic cells. 31 Similar studies have shown that ROS are also produced in cells undergoing apoptotic-like cell death, but that the produced ROS do not cause apoptosis. 32 In this study, we observed that ROS were not required to induce apoptosis in PTEN-proficient glioma.…”

Section: Discussionmentioning

confidence: 86%

PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation

et al. 2010

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Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) has frequently been observed in human gliomas, conferring AKT activation and resistance to ionizing radiation (IR) and drug treatments. Recent reports have shown that PTEN loss or AKT activation induces premature senescence, but many details regarding this effect remain obscure. In this study, we tested whether the status of PTEN determined fate of the cell by examining PTEN-deficient U87, U251, and U373, and PTEN-proficient LN18 and LN428 glioma cells after exposure to IR. These cells exhibited different cellular responses, senescence or apoptosis, depending on the PTEN status. We further observed that PTEN-deficient U87 cells with high levels of both AKT activation and intracellular reactive oxygen species (ROS) underwent senescence, whereas PTEN-proficient LN18 cells entered apoptosis. ROS were indispensable for inducing senescence in PTEN-deficient cells, but not for apoptosis in PTENproficient cells. Furthermore, transfection with wild-type (wt) PTEN or AKT small interfering RNA induced a change from premature senescence to apoptosis and depletion of p53 or p21 prevented IR-induced premature senescence in U87 cells. Our data indicate that PTEN acts as a pivotal determinant of cell fate, regarding senescence and apoptosis in IR-exposed glioma cells. We conclude that premature senescence could have a compensatory role for apoptosis in the absence of the tumor suppressor PTEN through the AKT/ROS/p53/p21 signaling pathway.

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Section: Discussionmentioning

confidence: 86%

PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation

et al. 2010

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“…Cell cycle arrest Previously, it was shown that a 4 h pulse of 0.25 μM of adriamycin induced senescence in MCF-7 cells (Song and Hwang, 2005). Adriamycin is a chemical that induces DNA scission through the generation of hydroxyl radicals (Berlin and Haseltine, 1981), and it has been reported to induce both G1 and G2/M arrest (De Vincenzo et al, 1996;Fornari et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

“…MCF-7 cells, a human breast cancer line, undergo senescence after a pulse of a moderate dose of adriamycin (doxorubicin) (Elmore et al, 2002;Song and Hwang, 2005). In the present study, a time-course study was carried out on the levels of the senescence phenotypes expressed in the adriamycin-treated MCF-7 cells.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of the Cell Biological Changes Occurring in the Progression of DNA Damage-Induced Senescence

Cho

Park

Hwang

2011

Molecules and Cells

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“…Detection of Reactive Oxygen Generation Dichlorofluorescein diacetate was used to detect ROS following exposure to EB 1089 and radiation (21). MCF-7 cells were seeded in T-25 flasks and treated as described in the cell viability study above.…”

Section: Terminal Deoxynucleotidyl Transferase^mediated Dutp Nick Endmentioning

confidence: 99%

Potentiation of radiation sensitivity in breast tumor cells by the vitamin D3 analogue, EB 1089, through promotion of autophagy and interference with proliferative recovery

DeMasters

Newsham

et al. 2006

Molecular Cancer Therapeutics

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Abstract1,25-Dihydroxyvitamin D 3 and vitamin D 3 analogues, such as EB 1089, potentiate the response to ionizing radiation in breast tumor cells. The current studies address the basis for this interaction by evaluating DNA damage and repair, the effect of interference with reactive oxygen generation, the involvement of p53 and caspase-3, signaling through c-myc, as well as the induction of senescence and multiple modes of cell death. EB 1089 failed to increase the extent of radiation-induced DNA damage or to attenuate the rate of DNA repair. The reactive oxygen scavengers N-acetyl-L-cysteine and reduced glutathione failed to protect the cells from the promotion of cell death by EB 1089 and radiation. Whereas MCF-7 cells expressing caspase-3 showed significant apoptosis with radiation alone as well as with EB 1089 followed by radiation, EB 1089 maintained its ability to confer susceptibility to radiation-induced cell killing, in large part by interference with proliferative recovery. In contrast, in breast tumor cells lacking p53, where radiation promoted extensive apoptosis and the cells failed to recover after radiation treatment, EB 1089 failed to influence the effect of radiation. EB 1089 treatment interfered with radiationinduced suppression of c-myc; however, induction of c-myc did not prevent senescence by radiation alone or radiation-induced cell death promoted by EB 1089. EB 1089 did not increase the extent of micronucleation, indicative of mitotic catastrophe, induced by radiation alone. However, EB 1089 did promote extensive autophagic cell death in the irradiated cells. Taken together, these studies suggest that the effect of EB 1089 treatment on the radiation response is related in part to enhanced promotion of autophagic cell death and in part to interference with the proliferative recovery that occurs with radiation alone in p53 wild-type breast tumor cells.

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Dinstinct ROS and biochemical profiles in cells undergoing DNA damage-induced senescence and apoptosis

Cited by 79 publications

References 46 publications

PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation

PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation

Kinetics of the Cell Biological Changes Occurring in the Progression of DNA Damage-Induced Senescence

Potentiation of radiation sensitivity in breast tumor cells by the vitamin D3 analogue, EB 1089, through promotion of autophagy and interference with proliferative recovery

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