CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

Desai, Amar; Webb, Bryan M.; Gerson, Stanton L.

doi:10.1016/j.radonc.2013.10.040

Cited by 98 publications

(74 citation statements)

References 39 publications

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“…Upon irradiation, these cells showed the ability to self-renew and generate differentiated progeny (Gomez-Casal et al, 2013). Similar results were obtained by another group that revealed substantial expansion of the lung adenoma CSC population following irradiation, characterized by a two-fold increase in resistance to IR (Desai et al, 2014a). Furthermore, lung ADC CSCs were shown to possess high migration and invasion capacity (Zhang et al, 2014a) and diminished apoptotic response in vitro and in vivo (Lundholm et al, 2013).…”

Section: Radioresistance Of Lung Adenocarcinomasupporting

confidence: 76%

“…Similarly, degradation of the DNA damage response protein -human single-strand DNA binding protein 1 caused increased sensitivity to IR via impairment of DSB repair (Chen et al, 2015). Silencing of two homologous recombination genes, exonuclease1 and Rad51, resulted in complete loss of lung ADC cells' expansion and increased radiation sensitivity (Desai et al, 2014a). These data indicate an important role for DNA damage repair in the radioresistance of lung ADC cells.…”

Section: Radioresistance Of Lung Adenocarcinomamentioning

confidence: 88%

“…Increased DNA damage repair capacity is a common feature of many types of cancer and plays an important role in clinical outcome (Curtin, 2012). RT-resistant lung ADC cells were shown to have upregulated expression of DSB repair genes and enhanced DSB repair capacity (Desai et al, 2014a, Mihatsch et al, 2011. Specific inhibition of DNA-dependent protein kinase and poly-adenosine diphosphate [ADP]-ribose polymerase proteins involved in DNA DSB repair significantly increased the sensitivity of ADC cells to IR, inhibited clonogenic survival and induced prosenescent properties of IR in vitro and in vivo (Azad et al, 2014).…”

Section: Radioresistance Of Lung Adenocarcinomamentioning

confidence: 99%

See 2 more Smart Citations

Cell death in cancer therapy of lung adenocarcinoma

Zagryazhskaya

Gyurászová²,

Zhivotovsky

2015

Int. J. Dev. Biol.

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Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio-and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.

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Section: Radioresistance Of Lung Adenocarcinomasupporting

confidence: 76%

Section: Radioresistance Of Lung Adenocarcinomamentioning

confidence: 88%

Section: Radioresistance Of Lung Adenocarcinomamentioning

confidence: 99%

See 1 more Smart Citation

Cell death in cancer therapy of lung adenocarcinoma

Zagryazhskaya

Gyurászová²,

Zhivotovsky

2015

Int. J. Dev. Biol.

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“…In addition to glioma stem cells, enhanced DNA repair capacity was also found in other CSCs. For example, enhanced repair of DNA DSBs and upregulated expression of DSB repair genes were found in CD133+ CSCs isolated from the A549 human lung carcinoma cell line [40] . Similarly, DDR and the expression of various repair proteins are also found to be highly up-regulated in [50] , which may also exhibit different DDR.…”

Section: Ddr In Cscsmentioning

confidence: 99%

DNA damage responses in cancer stem cells: Implications for cancer therapeutic strategies

Wang

2015

WJBC

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The identification of cancer stem cells (CSCs) that are responsible for tumor initiation, growth, metastasis, and therapeutic resistance might lead to a new thinking on cancer treatments. Similar to stem cells, CSCs also display high resistance to radiotherapy and chemotherapy with genotoxic agents. Thus, conventional therapy may shrink the tumor volume but cannot eliminate cancer. Eradiation of CSCs represents a novel therapeutic strategy. CSCs possess a highly efficient DNA damage response (DDR) system, which is considered as a contributor to the resistance of these cells from exposures to DNA damaging agents. Targeting of enhanced DDR in CSCs is thus proposed to facilitate the eradication of CSCs by conventional therapeutics. To achieve this aim, a better understanding of the cellular responses to DNA damage in CSCs is needed. In addition to the protein kinases and enzymes that are involved in DDR, other processes that affect the DDR including chromatin remodeling should also be explored.

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“…+ lung cancer cells are stem-like cancer cells, and this group of lung cancer cells is reported to be resistant to anti-cancer treatment [34,35]. [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Imperatorin Targets MCL-1 to Sensitize CD133+ Lung Cancer Cells to γδ-T Cell-Mediated Cytotoxicity

You

Gao

2018

Cell Physiol Biochem

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Background/Aims: CD133⁺ cancer cells display low sensitivity to anti-cancer treatment; thus, combination treatment with adjuvant drugs is required to improve the efficiency of cancer therapy. The aim of this study was to explore the effect of imperatorin, a linear furanocoumarin compound, on γδ T cell-mediated cytotoxicity against CD133⁺ lung cancer cells. Methods: CD133⁺ and CD133^- subgroups from A549 and PC9 lung cancer cells were sorted by using flow cytometry. The cytotoxicity of γδ T cells against cancer cells was evaluated by measuring lactate dehydrogenase release. The concentration of tumor necrosis factor-related apoptosis-inducing ligand in the co-culture system was determined by using an enzyme-linked immunosorbent assay. Mitochondrial membrane potential, expression of death receptor 4 (DR4) and DR5 on the cell surface, and rate of apoptosis were measured by flow cytometry. Cytochrome c release and cellular protein expression were detected by western blot analysis. Results: Compared with CD133^- cells, CD133⁺ cells were resistant to γδ T cell-mediated cytotoxicity. However, imperatorin significantly increased the sensitivity of CD133⁺ lung cancer cells to γδ T cell treatment in vitro and in vivo. Mechanically, we found that myeloid cell leukemia 1 (MCL-1), an important anti-apoptotic protein belonging to the Bcl-2 family, was overexpressed in CD133⁺ A549 and PC9 cells compared to their corresponding CD133^- cells. Co-treatment with imperatorin and γδ T cells suppressed the expression of MCL-1, and thus promoted the mitochondrial apoptosis mediated by γδ T cells in CD133⁺ A549 and PC9 lung cancer cells. Conclusion: Up-regulated MCL-1 in CD133⁺ lung cancer cells is responsible for their resistance to γδ T cells. Furthermore, the combination of γδ T cells with imperatorin sensitized CD133⁺ lung cancer cells to γδ T cell-mediated cytotoxicity by targeting MCL-1.

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CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

Cited by 98 publications

References 39 publications

Cell death in cancer therapy of lung adenocarcinoma

Cell death in cancer therapy of lung adenocarcinoma

DNA damage responses in cancer stem cells: Implications for cancer therapeutic strategies

Imperatorin Targets MCL-1 to Sensitize CD133+ Lung Cancer Cells to γδ-T Cell-Mediated Cytotoxicity

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