Low doses of ionizing radiation suppress doxorubicin-induced senescence-like phenotypes by activation of ERK1/2 and suppression of p38 kinase in MCF7 human breast cancer cells

Shin, Jae-Sik; Woo, Seung Kyoon; Lee, Hyung-Chahn; Hong, Seung-Woo; Yoo, Doo-Hyun; Hong, Seok‐Il; Lee, Wang-Jae; Jin, Young-Woo; An, Sungkwan; Jin, Dong-Hoon; Park, In-Chul

doi:10.3892/ijo_00000630

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…While, chrysin showed antiproliferative activity by suppressing p38 MAPK expression, which involved JNK and NF-κB in cardiac cells [ 102 ]. Exposure to low dose of ionizing radiation was found to suppress cancer cell proliferation via suppressing p38 kinase in MCF-7 human breast cancer cells [ 103 ], inhibiting JNK as well as ERK phosphorylation [ 87 ], and down-regulating NF-κB through suppressing TNFα-induced degradation of inhibitor of kappa B (IκB) protein and release of p65 subunit to the nucleus, reducing NF-κB activity [ 104 ].…”

Section: Discussionmentioning

confidence: 99%

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways

Abdelhakm

Kandil

Mansour

et al. 2023

Biol Trace Elem Res

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Improving radiation effect on tumor cells using radiosensitizers is gaining traction for improving chemoradiotherapy. This study aimed to evaluate copper nanoparticles (CuNPs) synthesized using chrysin as radiosensitizer with γ-radiation on biochemical and histopathological approaches in mice bearing Ehrlich solid tumor. CuNPs were characterized with irregular round sharp shape with size range of 21.19–70.79 nm and plasmon absorption at 273 nm. In vitro study on MCF-7 cells detected cytotoxic effect of CuNPs with IC50 of 57.2 ± 3.1 μg. In vivo study was performed on mice transplanted with Ehrlich solid tumor (EC). Mice were injected with CuNPs (0.67 mg/kg body weight) and/or exposed to low dose of gamma radiation (0.5 Gy). EC mice exposed to combined treatment of CuNPs and radiation showed a marked reduction in tumor volume, ALT and CAT, creatinine, calcium, and GSH, along with elevation in MDA, caspase-3 in parallel with inhibition of NF-κB, p38 MAPK, and cyclin D1 gene expression. Comparing histopathological findings of treatment groups ends that combined treatment was of higher efficacy, showing tumor tissue regression and increase in apoptotic cells. In conclusion, CuNPs with a low dose of gamma radiation showed more powerful ability for tumor suppression via promoting oxidative state, stimulating apoptosis, and inhibiting proliferation pathway through p38MAPK/NF-κB and cyclinD1.

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Section: Discussionmentioning

confidence: 99%

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways

Abdelhakm

Kandil

Mansour

et al. 2023

Biol Trace Elem Res

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“…AKT, ERK, MAPKs and PKC have been shown to be involved in CDK1, CDK2 and cyclin D regulation in various cell types [13][14][15][16][17]. In order to examine whether the activities of AKT, ERK, MAPKs and PKC are affected by combined treatment with Dox and Tam, the phosphorylation of Akt, ERK, MAPKs and PKC in BT483 cells was analyzed after combined treatment with Dox and Tam for 12 h and 24 h. In (Figure 6), combined treatment with Dox and Tam synergistically increases ERK phosphorylation.…”

Section: Combined Treatment With Dox and Tam Modulated The Phosphorylmentioning

confidence: 99%

The use of a combination of tamoxifen and doxorubicin synergistically to induce cell cycle arrest in BT483 cells by down-regulating CDK1, CDK2 and cyclin D expression

Chuang¹,

Huang²,

Huang³

2013

J Pharm Technol Drug Res

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Background: Tamoxifen and Doxorubicin are used alone or in combination to treat breast cancer. Although these drugs have been utilized in combination, the advantage of their combination, in terms of therapeutic efficacy, still remains controversial. Methods: Cells were treated with Tamoxifen alone and doxorubicin alone or treated with both Tamoxifen and doxorubicin, cell cycle distribution, cell cycle regulatory protein, mRNA, and activity were measured. Results: This study uses breast cancer cell lines to demonstrate the synergistic interaction between Doxorubicin and Tamoxifen, and to explain the CDK1 and CDK2 expression underlying the synergy. This study demonstrates that the combination of Doxorubicin and Tamoxifen significantly reduces the growth of ER-positive breast cancer cells and that this is driven primarily by the enhanced effect of the decreased protein expression of the CDK1, CDK2 and cyclin D. It is also proposed that selective modification of AKT inactivation, ERK activation probably contributes to the synergistic interaction. Conclusions: Overall, the findings suggest that a combination of Doxorubicin and Tamoxifen could be effective in the treatment of ER-positive breast cancers, so this combination warrants further investigation.

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Simvastatin treatment varies the radiation response of human breast cells in 2D or 3D culture

et al. 2020

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SummaryBackground Statins inhibit the cholesterol biosynthesis and are used as cholesterol-lowering agents in fat-metabolism disorders. Furthermore, several studies state that statins have supportive functions in breast cancer treatment. Therefore, simvastatin (SVA) as a potential radiosensitizer should be investigated on the basis of human breast cells. Methods First, an optimal concentration of SVA for normal (MCF10A) and cancer (MCF-7) cells was identified via growth and cytotoxicity assays that, according to the definition of a radiosensitizer in the narrower sense, enhances the effect of radiation therapy but has no cytotoxic effect. Next, in combination with radiation SVA’s influence on DNA repair capacity and clonogenic survival in 2D and 3D was determined. Furthermore cell cycle distribution, expression of survivin and connective tissue growth factor (CTGF) as well as ERK1 map kinase were analysed. Results 1 μM SVA was identified as highest concentration without an influence on cell growth and cytotoxicity and was used for further analyses. In terms of early and residual γH2AX-foci, SVA affected the number of foci in both cell lines with or without irradiation. Different radiation responses were detected in 2D and 3D culture conditions. During the 2D cultivation, a radiosensitizing effect within the clonogenic survival was observable, but not in 3D. Conclusion The present study suggests that SVA may have potential for radiosensitization. Therefore, it is important to further investigate the role of SVA in relation to the extent of radiosensitization and how it could be used to positively influence the therapy of breast cancer or other entities.

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Low doses of ionizing radiation suppress doxorubicin-induced senescence-like phenotypes by activation of ERK1/2 and suppression of p38 kinase in MCF7 human breast cancer cells

Cited by 5 publications

References 28 publications

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways

The use of a combination of tamoxifen and doxorubicin synergistically to induce cell cycle arrest in BT483 cells by down-regulating CDK1, CDK2 and cyclin D expression

Simvastatin treatment varies the radiation response of human breast cells in 2D or 3D culture

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