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

Liu, Mu-Tai; Reíter, Russel J.

doi:10.15761/nmbi.1000127

Cited by 3 publications

(2 citation statements)

References 167 publications

(243 reference statements)

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“…As expected, melatonin at high doses decreased the proliferation rate and increased ROS levels and apoptosis in patient-derived cell culture, as well as completely abolishing spheroid formation, which are considered a CSC marker [23,41]. These results appear to be congruent with other studies showing that melatonin suppresses CSC-like phenotypes in other types of cancer [58,59]. Moreover, intratumoral melatonin also reduced tumor volumes in PDXs, which represent a promising pre-clinical model that can be used to predict drug responses [18].…”

Section: Discussionsupporting

confidence: 89%

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

Martínez-Ruiz

Florido

Rodríguez-Santana

et al. 2023

Preprint

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The prognosis of head and neck squamous cell carcinoma (HNSCC) remains poor, with a high mortality rate. Melatonin has been shown to have oncostatic effects in different types of cancers. However, inconsistent results have been reported for in vivo applications, which may depend on the low bioavailability of melatonin to the tumor. Consequently, an alternative administration route is needed to improve bioavailability and establish the optimal dosage of melatonin for cancer treatment. On the other hand, the use of patient-derived tumor tissues has transformed the field of drug research because they reflect the heterogeneity of patient tumor tissues. In the present study, we explore mechanisms for increasing melatonin bioavailability in tumors and investigate its potential as an adjuvant to improve the therapeutic efficacy of cisplatin (CDDP) in the setting of both xenotransplanted cell lines and primary human HNSCC. We analyzed the effect of two different formulations of melatonin administered subcutaneously or intratumorally in Cal-27 and SCC-9 xenografts and in patient-derived xenografts, which more closely resemble real tumors. In contrast to the results obtained with the subcutaneous administration of melatonin, intratumoral injection of melatonin drastically inhibited tumor progression in HNSCC-derived xenografts, as well as in patient-derived xenografts, suggesting that high doses of melatonin are necessary to exert its oncostatic effect. Interestingly, intratumoral injection of melatonin potentiated CDDP effects, decreasing Cal-27 tumor growth. Specifically, we demonstrated that melatonin increases ROS production and apoptosis in tumors, targeting tumor mitochondria, which had a more elongated morphology and cytoplasmic distribution than mitochondria in control tumors. Melatonin also reduces migration capacities and metastasis markers. These results illustrate the great clinical potential of intratumoral melatonin treatment and encourage a future clinical trial in cancer patients to establish a new melatonin treatment with proper clinical applications.

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Section: Discussionsupporting

confidence: 89%

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

Martínez-Ruiz

Florido

Rodríguez-Santana

et al. 2023

Preprint

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“…Nevertheless, the expression of ABCG2 was quantified to be reduced. The reduction in the expression level of ABCG2 is a result of the methylation of its promoter by the action of melatonin to overcome drug resistance 35 .…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative effect of melatonin in human hepatoma HepG2 cells occurs mainly through cell cycle arrest and inflammation inhibition

Nabih

Hamed

Yahya

2023

Sci Rep

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Hepatocellular carcinoma (HCC) is the major lethal primary liver malignant worldwide. Although, melatonin has various antitumor bioactivities; there is a requirement for more investigations to elucidate the not discussed effects, and the controversial responses of the treatment with melatonin on targets mediated in HCC. To achieve the aim of the present study, HCC-HepG2 cells were treated with different concentrations of melatonin at various time intervals. The selected minimal proliferation inhibition doses of melatonin were then incubated with cells to examine the arresting effect of melatonin on dividing cells using flow cytometry. Furthermore, the molecular patterns of genes that contributed to apoptosis, drug resistance development, antioxidation, and melatonin crossing were quantified by qRT-PCR. Additionally, the Human inflammation antibody array membrane (40 targets) was used to check the anti-inflammatory effect of melatonin. Our results validated that, melatonin shows anti-proliferative action through preserving cells in G0/G1 phase (P < 0.001) that is associated with a highly significant increase in the expression level of the P53 gene (P < 0.01). On contrary, as a novelty, our data recorded decreases in expression levels of genes involved in the pro-apoptotic pathway; with a significant increase (P < 0.05) in the expression level of an anti-apoptotic gene, Bcl2. Interestingly, we detected observed increases in the expression levels of genes responsible for conferring drug resistance including ABCB1, ABCC1, and ABCC5. Our study proved the anti-inflammatory activity of 1 mM melatonin in HCC-HepG2 cells. Accordingly, we can conclude that melatonin facilitates the anti-proliferation of cells at doses of 1 mM, and 2.5 mM after 24 h. This action is initiated through cell cycle arrest at G0/G1 phase via increasing the expression of P53, but independently on apoptosis. Collectively, melatonin is an effective anti-inflammatory and anti-proliferative promising therapy for the treatment of HCC. However, its consumption should be cautious to avoid the development of drug resistance and provide a better treatment strategy.

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Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

Martinez-Ruiz,

Florido,

Rodriguez-Santana

et al. 2023

Biomedicine & Pharmacotherapy

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

Cited by 3 publications

References 167 publications

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

Anti-proliferative effect of melatonin in human hepatoma HepG2 cells occurs mainly through cell cycle arrest and inflammation inhibition

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

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