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Article

Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches

by
Claudio Tabolacci
1,*,
Martina Cordella
1,
Stefania Rossi
1,
Marialaura Bonaccio
2,
Adriana Eramo
1,
Carlo Mischiati
3,
Simone Beninati
4,
Licia Iacoviello
2,5,
Antonio Facchiano
6,† and
Francesco Facchiano
1,†
1
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
2
Department of Epidemiology and Prevention, IRCCS Neuromed, 86077 Pozzilli, Italy
3
Department of Neuroscience and Rehabilitation, School of Medicine, University of Ferrara, 44121 Ferrara, Italy
4
Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy
5
Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, 21100 Varese-Como, Italy
6
Laboratory of Molecular Oncology, IDI-IRCCS, 00167 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2021, 26(12), 3619; https://doi.org/10.3390/molecules26123619
Submission received: 10 May 2021 / Revised: 8 June 2021 / Accepted: 9 June 2021 / Published: 13 June 2021
(This article belongs to the Special Issue Antiproliferative and Anti-inflammatory Activities of Plant-Derived Compounds)
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Abstract

The beneficial effects of coffee on human diseases are well documented, but the molecular mechanisms of its bioactive compounds on cancer are not completely elucidated. This is likely due to the large heterogeneity of coffee preparations and different coffee-based beverages, but also to the choice of experimental models where proliferation, differentiation and immune responses are differently affected. The aim of the present study was to investigate the effects of one of the most interesting bioactive compounds in coffee, i.e., caffeine, using a cellular model of melanoma at a defined differentiation level. A preliminary in silico analysis carried out on public gene-expression databases identified genes potentially involved in caffeine’s effects and suggested some specific molecular targets, including tyrosinase. Proliferation was investigated in vitro on human melanoma initiating cells (MICs) and cytokine expression was measured in conditioned media. Tyrosinase was revealed as a key player in caffeine’s mechanisms of action, suggesting a crucial role in immunomodulation through the reduction in IL-1β, IP-10, MIP-1α, MIP-1β and RANTES secretion onto MICs conditioned media. The potent antiproliferative effects of caffeine on MICs are likely to occur by promoting melanin production and reducing inflammatory signals’ secretion. These data suggest tyrosinase as a key player mediating the effects of caffeine on melanoma.
Keywords: caffeine; melanoma; melanin; immunomodulatory signals; bioactive compounds caffeine; melanoma; melanin; immunomodulatory signals; bioactive compounds
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MDPI and ACS Style

Tabolacci, C.; Cordella, M.; Rossi, S.; Bonaccio, M.; Eramo, A.; Mischiati, C.; Beninati, S.; Iacoviello, L.; Facchiano, A.; Facchiano, F. Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches. Molecules 2021, 26, 3619. https://doi.org/10.3390/molecules26123619

AMA Style

Tabolacci C, Cordella M, Rossi S, Bonaccio M, Eramo A, Mischiati C, Beninati S, Iacoviello L, Facchiano A, Facchiano F. Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches. Molecules. 2021; 26(12):3619. https://doi.org/10.3390/molecules26123619

Chicago/Turabian Style

Tabolacci, Claudio, Martina Cordella, Stefania Rossi, Marialaura Bonaccio, Adriana Eramo, Carlo Mischiati, Simone Beninati, Licia Iacoviello, Antonio Facchiano, and Francesco Facchiano. 2021. "Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches" Molecules 26, no. 12: 3619. https://doi.org/10.3390/molecules26123619

APA Style

Tabolacci, C., Cordella, M., Rossi, S., Bonaccio, M., Eramo, A., Mischiati, C., Beninati, S., Iacoviello, L., Facchiano, A., & Facchiano, F. (2021). Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches. Molecules, 26(12), 3619. https://doi.org/10.3390/molecules26123619

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