摘要：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. Results: The collected data included the impact of melatonin and carbon ion irradiation on tumor stem cells. The impact of melatonin on tumor stem cells consisted of ‘Melatonin inhibits tumorigenicity of brain tumor stem cells via the AKT-EZH2-STAT3 signaling axis’, ‘Melatonin-induced methylation of the ABCG2/BCRP promoter overcomes multidrug resistance in brain tumor stem cells’, ‘Involvement of autophagy in melatonin-induced cytotoxicity in brain tumor stem cells’, ‘Melatonin inhibits estrogen receptor binding to estrogen response elements sites on the OCT4 gene in breast cancer stem cells’ and ‘Effect of melatonin in epithelial mesenchymal transition markers and invasive properties of breast cancer stem cells’. The impact of carbon ion irradiation on tumor stem cells consisted of ‘Carbon ion irradiation effectively eradicates brain tumor stem cells’, ‘Carbon ion irradiation counteracts cancer stem cells' migration and invasion process in head and neck squamous cell carcinoma’, ‘Carbon ion beam combined with cisplatin effectively disrupts triple negative breast cancer stem cells’, ‘Effects of carbon ion beam on putative colon cancer stem cells and its comparison with X-rays’ and ‘Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells’. 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-stem-like 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.
关键词：Melatonin; X-ray irradiation; charged particle irradiation; carbon ion irradiation; cancer stem cells; tumor-initiating cells; cancer stem-like cells
