Regulation of Apoptosis and Radiation Sensitization in Lung Cancer Cells via the Sirt1/NF-κB/Smac Pathway

Ji, Kaihua; Sun, Xinwei; Liu, Yang; Du, Liqing; Wang, Yan; He, Ningning; Wang, Jinhan; Xu, Chang; Liu, Qiang

doi:10.1159/000491730

Cited by 33 publications

(15 citation statements)

References 51 publications

(62 reference statements)

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“…The same effect was also observed with other mTOR inhibitors including temsirolimus, everolimus, curcumin, and epigallocatechin gallate [214]. Conversely, resveratrol (50 μM) protected lung cancer cell lines A549 and H460 against radiation-induced apoptosis through Sirt1 activation [215].…”

Section: Other Cardiotoxic Cancer Treatmentsmentioning

confidence: 75%

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

2019

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Cardio-oncology is a clinical/scientific discipline which aims to prevent and/or treat cardiovascular diseases in cancer patients. Although a large number of cancer treatments are known to cause cardiovascular toxicity, they are still widely used because they are highly effective. Unfortunately, therapeutic interventions to prevent and/or treat cancer treatment-induced cardiovascular toxicity have not been established yet. A major challenge for such interventions is to protect the cardiovascular system without compromising the therapeutic benefit of anticancer medications. Intriguingly, the polyphenolic natural compound resveratrol and its analogs have been shown in preclinical studies to protect against cancer treatment-induced cardiovascular toxicity. They have also been shown to possess significant anticancer properties on their own, and to enhance the anticancer effect of other cancer treatments. Thus, they hold significant promise to protect the cardiovascular system and fight the cancer at the same time. In this review, we will discuss the current knowledge regarding the cardio-protective and the anticancer properties of resveratrol and its analogs. Thereafter, we will discuss the challenges that face the clinical application of these agents. To conclude, we will highlight important gaps of knowledge and future research directions to accelerate the translation of these exciting preclinical findings to cancer patient care.

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Section: Other Cardiotoxic Cancer Treatmentsmentioning

confidence: 75%

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

2019

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“…Proteins associated with these aggressive behaviors, such as cyclin D1, Bcl-2 and MMP-9, are regulated by a key transcriptional factor, NF-κB. NF-κB activity modulates the balance between RT-induced apoptosis and radioresistance that influences the efficacy of RT in certain types of cancer, including oropharyngeal cancer, HCC and lung cancer (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

A combination of sorafenib and radiotherapy reduces NF‑κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model

et al. 2021

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Hepatocellular carcinoma (HCC) is difficult to diagnose at an early stage, and its prognosis is generally poor. Sorafenib is the primary treatment for unresectable advanced HCC and targets multiple receptor tyrosine kinases. However, sorafenib only extends the average survival time by 3 months. This observation indicates that sorafenib may need to be combined with other treatments to further improve outcomes. We previously showed that combination of sorafenib with radiotherapy (RT) enhances tumor inhibition in subcutaneous HCC mouse models compared with monotherapy. The present study demonstrated that combining sorafenib and RT could suppress tumor growth in an orthotopic HCC model by regulating apoptosis and N F-κ B-related pathways. Moreover, decreased numbers of visible liver tumors and a smaller percentage of spleen metastases were found in the combination group. A transient drop in body weight was initially observed after RT, but progressive recovery of body weight occurred. The current study showed that the combination of sorafenib and RT could be a safe strategy for HCC treatment.

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“…It is involved in the pathway Sirt1/NF-κB/Smac associated with radiation damage. 35 Dclre1c (DNA cross-link repair 1C) is also a target gene involved in the repair of DNA damage caused by radiation. ATG5 is an autophagy-related gene.…”

Section: Discussionmentioning

confidence: 99%

Exosomal Small RNA Sequencing Uncovers Dose-Specific MiRNA Markers for Ionizing Radiation Exposure

et al. 2020

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Introduction: Acute exposure to ionizing radiation (IR) is hazardous or even lethal. Accurate estimation of the doses of IR exposure is critical to wisely determining the following treatments. Exosomes are nanoscale vesicles harboring biomolecules and mediate the communications among cells and tissues to influence biological processes. Screening out the microRNAs (miRNAs) contained in exosomes as biomarkers can be useful for estimating the IR exposure doses and exploring the correlation between these miRNAs and the occurrence of disease. Methods: We treated mice with 2.0, 6.5, and 8.0 Gy doses of IR and collected the mice sera at 0, 24, 48, and 72 hours after exposure. Then, the serum exosomes were isolated by ultracentrifuge and the small RNA portion was extracted for sequencing and the following bioinformatics analysis. Qualitative polymerase chain reaction was performed to validate the potential dose-specific markers. Results: Fifty-six miRNAs (31 upregulated, 25 downregulated) were differentially expressed after exposure of the above 3 IR doses and may act as common IR exposure miRNA markers. Bioinformatic analysis also identified several dosage-specific responsive miRNAs. Importantly, IR-induced miR-151-3p and miR-128-3p were significantly and stably increased at 24 hours in different mouse strains with distinct genetic background after exposed to 8.0 Gy of IR. Conclusion: Our study shows that miR-151-3p and miR-128-3p can be used as dose-specific biomarkers of 8.0 Gy IR exposure, which can be used to determine the exposure dose by detecting the amount of the 2 miRNAs in serum exosomes.

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Regulation of Apoptosis and Radiation Sensitization in Lung Cancer Cells via the Sirt1/NF-κB/Smac Pathway

Cited by 33 publications

References 51 publications

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

A combination of sorafenib and radiotherapy reduces NF‑κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model

Exosomal Small RNA Sequencing Uncovers Dose-Specific MiRNA Markers for Ionizing Radiation Exposure

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