Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells

Oonishi, Kazuhiko; Chen, Xing; Hirakawa, Hirokazu; Fujimori, A.; Yamada, Shigeru; Yokosuka, Osamu; Kamada, Tadashi

doi:10.1016/j.radonc.2012.08.009

Cited by 82 publications

(109 citation statements)

References 24 publications

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“…As compared with photon irradiation, a higher percentage (2.4-fold) of GSCs stained positive for nuclear γ-H2AX 24 hours after carbon ion irradiation, demonstrating residual unrepaired double-strand breaks. Likewise, carbon ion irradiation increased persistent γ-H2AX foci as compared with photon irradiation in putative pancreatic stem cells (32,106). These results indicate that the sensitivity of cancer stem cells to carbon ions might exhibit an impaired capability of GSCs to repair carbon ion-induced DNA double-strand breaks.…”

Section: The Impact Of Carbon Ion Irradiation On Tumor Stem Cells Carmentioning

confidence: 79%

“…The number of radiation induced γH2AX foci is closely related to the number of DSB (164,165). Slowly repaired or unrepaired DSB may account for cell death [32,166]. Carbon ion irradiation is regarded as a more effective therapy than X-ray irradiation owing to the high RBE, the lack of the oxygen effect, and less cell cycle-related radiosensitivity [32,167].…”

Section: Effects Of Carbon Ion Beam On Putative Colon Cancer Stem Celmentioning

confidence: 99%

“…Slowly repaired or unrepaired DSB may account for cell death [32,166]. Carbon ion irradiation is regarded as a more effective therapy than X-ray irradiation owing to the high RBE, the lack of the oxygen effect, and less cell cycle-related radiosensitivity [32,167]. Furthermore, some studies have demonstrated that DSBs induced by heavy ion irradiation are repaired with slow kinetics compared to those induced by photon irradiation [168].…”

Section: Effects Of Carbon Ion Beam On Putative Colon Cancer Stem Celmentioning

confidence: 99%

“…Several recent studies indicate that carbon ion irradiation may be a promising therapeutic modality because of complex DNA damage, increased apoptosis, and counteractive actions on migration and invasive processes in both parental cells of head and neck squamous cell carcinoma and CSCs that it displays. This distinguishes it from photon irradiation [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

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The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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Aim: Cancer stem cells (CSCs) exhibited an excessive migratory and invasive potential. Melatonin may inhibit multiple crucial signals associated with tumor stem cell self-renewal, viability, invasiveness, tumor growth, and therapy resistance. Carbon ion irradiation may be a promising therapeutic modality in both non-stem-like and stem-like tumor cells in contrast to photon irradiation. A comprehensive understanding of the mechanisms and molecular pathways associated with invasive properties of CSCs is essential in developing novel treatment options for cancer therapy that target CSCs. Materials and methods:A systematic review of the existing literature was conducted using the following search terms: 'melatonin', 'X-ray irradiation', 'charged particle irradiation', 'carbon ion irradiation', 'cancer stem cells', 'tumor-initiating cells' and 'cancer stem-like cells'. The search used PubMed and spanned the period from January 2000 to December 2016. Conclusion:Cancer stem cells possess the capacity of self-renewal and pluripotency, generating all cells within a tumor, and are responsible for tumor growth, therapy resistance and metastasis. Melatonin attenuated AKT activation, EZH2 S21 phosphorylation, EZH2-STAT3 interactions and altered histone modifications to reduce tumor initiation and propagation of brain tumor stem cells (BTSC). Melatonin increases the efficacy of chemotherapeutic agents, targeting both the tumor bulk and BTSCs through the regulation of the expression and function of the ABCG2/BCRP transporter by inducing the methylation of its promoter. Melatonin treatment induced cell death with ultrastructural characteristics of autophagy. Breast cancer stem cells (BCSCs) are responsive to melatonin treatment by way of reducing the viability and the invasiveness of breast cancer mammospheres as well as regulating the expression of OCT4, N-cadherin and vimentin proteins associated with epithelial mesenchymal transition in BCSCs. Carbon irradiation is effective in brain tumor stem cell (BTSC) elimination with relative biologic effectiveness (RBE) in the range of 1.87-3.44. Carbon ion irradiation may be a promising therapeutic modality because it reduces migration and invasion processes in both head and neck squamous cell carcinoma and cancer stem cells in contrast to photon irradiation. Low LET X-ray irradiation may essentially eradicate the non-stem-like tumor cells, consequently the radioresistant cancer stem-like cell population is obviously enriched. In contrast, carbon ion irradiation may eradicate both non-stemlike and stem-like tumor cells at the same time. Carbon ion irradiation is a promising tool to eradicate putative colon cancer stem-like cells. Further investigation to elucidate the mechanisms and molecular pathways involved in cancer stem cells particularly associated with melatonin and carbon ion irradiation certainly is warranted.

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Section: The Impact Of Carbon Ion Irradiation On Tumor Stem Cells Carmentioning

confidence: 79%

Section: Effects Of Carbon Ion Beam On Putative Colon Cancer Stem Celmentioning

confidence: 99%

Section: Effects Of Carbon Ion Beam On Putative Colon Cancer Stem Celmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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“…Similar results were shown by follow-up studies. CD44 + / CD24 + have a significantly higher possibility for colony formation in vitro (43), and are more resistant to irradiation (43 (23). In addition, CD44, CD24, and EPCAM are now widely used for the identification of pancreatic cancer stem cells (28,(44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the β-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib

Wang

Shen

et al. 2015

International Journal of Oncology

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Abstract. Increasing evidence suggests that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth, and are hypothesized to account for therapeutic resistance. Based on the expression of the surface markers CD44, CD24, and EPCAM, putative CSCs have also been identified in pancreatic cancers. It has been well established that aberrant activation of β-catenin signaling pathway may contribute to the maintenance of CSCs. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. In our previous studies, we demonstrated that cantharidin treatment induced phosphorylation of β-catenin, leading to repression on β-catenin pathway. Therefore, in the present study, we investigated whether cantharidin and its derivant, norcantharidin, could repress the stemness of pancreatic cancer cells through repression on β-catenin pathway. By using microarray and flow cytometry, we found that treatment with cantharidin and norcantharidin repressed the expression of CD44, CD24, and EPCAM at both mRNA and protein levels, leading to decreased CD44 + /CD24 + /EPCAM + proportion, the putative pancreatic CSC subset. Pretreatment with the β-catenin pathway inhibitor FH535, attenuated the cantharidin-and norcantharidin-inducrd repression on CD44, CD24, and EPCAM, suggesting cantharidin and its derivant repressed stemness of pancreatic cancer cells in β-catenin pathway-dependent manner. Furthermore, cantharidin and norcantharidin strengthened the cytotoxicity of gemcitabine and erlotinib, two well established pharmacotherapeutics against pancreatic cancers, indicating cantharidin and norcantharidin could be promising candidates for reversing drug resistance in pancreatic cancers. In conclusion, we presently propose that cantharidin and norcantharidin hold their promise in pancreatic cancer therapy through repression on stemness and strengthening the cytotoxicity of the present therapeutics.

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Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

Zhang

Gan

et al. 2020

Journal Cellular Physiology

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Radiotherapy is one of the major modalities for malignancy treatment. High linear energy transfer (LET) charged-particle beams, like proton and carbon ions, exhibit favourable depth-dose distributions and radiobiological enhancement over conventional low-LET photon irradiation, thereby marking a new era in high precision medicine. Tumour cells have developed multicomponent signal transduction networks known as DNA damage responses (DDRs), which initiate cell-cycle checkpoints and induce double-strand break (DSB) repairs in the nucleus by nonhomologous end joining or homologous recombination pathways, to manage ionising radiation (IR)-induced DNA lesions. DNA damage induction and DSB repair pathways are reportedly dependent on the quality of radiation delivered. In this review, we summarise various types of DNA lesion and DSB repair mechanisms, upon irradiation with low and high-LET radiation, respectively. We also analyse factors influencing DNA repair efficiency. Inhibition of DNA damage repair pathways and dysfunctional cell-cycle checkpoint sensitises tumour cells to IR.

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Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells

Abstract: Carbon ion beam has superior potential to kill pancreatic cancer stem cell-like cells, and prolonged induction of DNA damage might be one of the pivotal mechanisms of its high radiobiological effects compared to X-rays.

Cited by 82 publications

References 24 publications

The impact of melatonin and carbon ion irradiation on cancer stem cells

The impact of melatonin and carbon ion irradiation on cancer stem cells

Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the β-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib

Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

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