Effect of Strontium Ranelate on Hydrogen Peroxide-Induced Apoptosis of CRL-11372 Cells

Şenköylü, Alpaslan; Yılmaz, Akın; Ergün, Mehmet Ali; İlhan, Mustafa; Şimşek, Ayşe; Altun, Necdet; Bölükbaşı, Selçuk; Menevşe, Sevda

doi:10.1007/s10528-008-9142-1

Cited by 8 publications

(4 citation statements)

References 26 publications

(34 reference statements)

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“…This indicates that in higher concentration, H 2 O 2 induces necrosis rather than apoptosis. These findings are similar with those of a few researchers who discovered that low concentrations of H 2 O 2 induced cell death with apoptotic morphologic evidence while high concentrations of H 2 O 2 induced cell death with no apoptotic evidence in osteoblast [ 49 , 50 ].…”

Section: Discussionsupporting

confidence: 91%

Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma

2016

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BackgroundGenetic aberrations have been identified in nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains elusive. There are increasing evidences that the apoptotic nuclease caspase-activated deoxyribonuclease (CAD) is one of the players leading to translocation in leukemia. Oxidative stress, which has been strongly implicated in carcinogenesis, is a potent apoptotic inducer. Most of the NPC etiological factors are known to induce oxidative stress. Although apoptosis is a cell death process, cells possess the potential to survive apoptosis upon DNA repair. Eventually, the surviving cells may carry rearranged chromosomes. We hypothesized that oxidative stress-induced apoptosis may cause chromosomal breaks mediated by CAD. Upon erroneous DNA repair, cells that survive apoptosis may harbor chromosomal rearrangements contributing to NPC pathogenesis. This study focused on the AF9 gene at 9p22, a common deletion region in NPC. We aimed to propose a possible model for molecular mechanism underlying the chromosomal rearrangements in NPC.ResultsIn the present study, we showed that hydrogen peroxide (H2O2) induced apoptosis in NPC (HK1) and normal nasopharyngeal epithelial (NP69) cells, as evaluated by flow cytometric analyses. Activity of caspases 3/7 was detected in H2O2-treated cells. This activity was inhibited by caspase inhibitor (CI). By nested inverse polymerase chain reaction (IPCR), we demonstrated that oxidative stress-induced apoptosis in HK1 and NP69 cells resulted in cleavages within the breakpoint cluster region (BCR) of the AF9 gene. The gene cleavage frequency detected in the H2O2-treated cells was found to be significantly higher than untreated control. We further found that treatment with CI, which indirectly inhibits CAD, significantly reduced the chromosomal breaks in H2O2-cotreated cells. Intriguingly, a few breakpoints were mapped within the AF9 region that was previously reported to translocate with the mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemia (ALL) patient.ConclusionsIn conclusion, our findings suggested that oxidative stress-induced apoptosis could be one of the mechanisms underlying the chromosomal rearrangements in NPC. CAD may play an important role in chromosomal cleavages mediated by oxidative stress-induced apoptosis. A potential model for oxidative stress-induced apoptosis mediating chromosomal rearrangements in NPC is proposed.

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Section: Discussionsupporting

confidence: 91%

Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma

2016

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“…At the end of the incubation times, cells were stained with a mixture of acridine orange (AO) and ethidium bromide (EtBr) (Sigma-Aldrich) as described previously. 10 Then the cells were immediately analyzed under a fluorescence microscope (Olympus B202, Japan) at a 490-nm excitation wavelength.…”

Section: Methodsmentioning

confidence: 99%

The DNA methyl transferase inhibitor, 5′-aza-2-deoxycitidine, enhances the apoptotic effect of Mevastatin in human leukemia HL-60 cells

et al. 2013

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Statins induce antiproliferative effects and apoptotic response in various cancer cell types. Moreover, they also sensitize tumor cell lines from different origins to many agents. We aimed to investigate possible effects of Mevastatin (Mev) alone and sequential treatment of 5′-aza-2-deoxycitidine (DAC) and Mev on HL-60 cell line using XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay, lactate dehydrogenase release assay, flourescence microscopy, DNA fragmentation analysis, determination of DNA synthesis rate, and active caspase-3 assay. Messenger RNA (mRNA) expression of apoptotic and antiapoptotic genes were also evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for BAX, BCL2, and XIAP genes and quantitative Real-time PCR for CASP3, CASP8, and CASP9 genes. We showed that treatment with Mev alone and DAC followed by Mev resulted in apoptotic response in a time- and dose-dependent manner. We also found that pretreatment with DAC sensitized HL-60 cells to Mev and caused more apoptotic cell death than Mev-alone treatment via caspase-3 activation and DNA fragmentation. Moreover, sequential addition of Mev after DAC diminished DNA synthesis rate more effectively than Mev-alone treatment. Furthermore, DAC pretreatment significantly increased CASP3 and CASP9 mRNA expression even with lower doses of Mev. BAX, BCL2, and XIAP gene mRNA levels were also found to be changed in the presence of DAC and Mev. Determination of the exact molecular effects of statins and DAC would allow us to identify new molecular targets to develop more effective treatment regimens for cancer.

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“…Notably, SRR has been shown to suppress inflammatory responses by inhibiting the production of pro-inflammatory cytokines 17 , 18 . Furthermore, it has demonstrated protective effects against oxidative stress-induced cell damage 19 , 20 and has been reported to modulate apoptosis in various cell types 21 . However, it is important to acknowledge that the use of SRR also has some drawbacks.…”

Section: Introductionmentioning

confidence: 99%

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

Sun,

Zhu,

Sun

et al. 2023

Int. J. Med. Sci.

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Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro . Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD.

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Effect of Strontium Ranelate on Hydrogen Peroxide-Induced Apoptosis of CRL-11372 Cells

Cited by 8 publications

References 26 publications

Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma

Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma

The DNA methyl transferase inhibitor, 5′-aza-2-deoxycitidine, enhances the apoptotic effect of Mevastatin in human leukemia HL-60 cells

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

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