Details

Autor(en) / Beteiligte

• Martinez-Ruiz, Laura
• Florido, Javier
• Rodriguez-Santana, César
• López-Rodríguez, Alba
• Guerra-Librero, Ana
• Fernández-Gil, Beatriz I.
• García-Tárraga, Patricia
• Garcia-Verdugo, José Manuel
• Oppel, Felix
• Sudhoff, Holger
• Sánchez-Porras, David
• Ten-Steve, Amadeo
• Fernández-Martínez, José
• González-García, Pilar
• Rusanova, Iryna
• Acuña-Castroviejo, Darío
• Carriel, Víctor
• Escames, Germaine

Titel

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

Ist Teil von

• Biomedicine & pharmacotherapy, 2023-11, Vol.167, p.115518-115518, Article 115518

Ort / Verlag

Elsevier Masson SAS

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Head and neck squamous cell carcinoma present 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. 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 models 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 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. Melatonin effects on tumor mitochondrial metabolism was also evaluated as well as melatonin actions on tumor cell migration. In contrast to the results obtained with the subcutaneous melatonin, intratumoral injection of melatonin drastically inhibited tumor progression in HNSCC-derived xenografts, as well as in patient-derived xenografts. Interestingly, intratumoral injection of melatonin potentiated CDDP effects, decreasing Cal-27 tumor growth. We demonstrated that melatonin increases ROS production and apoptosis in tumors, targeting mitochondria. 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 proper clinical melatonin treatment. [Display omitted] •High concentrations of melatonin completely abolish tumor growth.•Melatonin synergized the effects of cisplatin.•Intratumoral melatonin also reduces tumor formation in patient-derived models.•Melatonin induces changes in tumor mitochondrial morphology and distribution.