Archives of Dermatological Research

, Volume 303, Issue 3, pp 201–210 | Cite as

Inhibition of basal and ultraviolet B-induced melanogenesis by cannabinoid CB1 receptors: a keratinocyte-dependent effect

  • Sofia MaginaEmail author
  • Carina Esteves-Pinto
  • Eduardo Moura
  • Maria Paula Serrão
  • Daniel Moura
  • Stefania Petrosino
  • Vincenzo Di Marzo
  • Maria Augusta Vieira-Coelho
Original Paper


Ultraviolet radiation is the major environmental insult to the skin and stimulates the synthesis of melanin in melanocytes, which then distribute it to the neighboring keratinocytes where it confers photo-protection. Skin color results from the paracrine interaction between these two cell types. Recent studies suggest that endocannabinoids are potential mediators in the skin. Here, we investigated whether cannabinoid drugs play a role in melanogenesis and if ultraviolet radiation modifies the cutaneous endocannabinoid system. We used human melanotic melanoma cell line (SK-mel-1) in monoculture or co-culture with human keratinocytes (HaCat). Endocannabinoid levels, cannabinoid receptors expression, and melanin content were evaluated under basal conditions and after ultraviolet-B irradiation (311 nm). We provide evidence that human melanoma cells (SK-mel-1) express CB1 receptors, and when in co-culture with keratinocytes (HaCat), the selective CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA 1 and 10 μM) inhibited (by 33.4 and 37.3%, respectively) basal melanogenesis. In addition, ultraviolet-B-induced melanogenesis in co-cultures was abolished by ACEA 10 μM. Both ACEA inhibitory effects were reversed by AM251 (1 μM), a selective CB1 antagonist. Furthermore, ultraviolet-B radiation increased endocannabinoids levels only in keratinocytes, whereas CB1 cannabinoid receptor expression was up-regulated only in melanoma cells. Our results collectively suggest that ultraviolet radiation activates paracrine CB1-mediated endocannabinoid signaling to negatively regulate melanin synthesis. The endocannabinoid system in the skin may be a possible target for future therapies in pigmentary disorders.


Melanin Melanoma Ultraviolet radiation Cannabinoids Co-culture 



The authors wish to thank Fabiana Piscitelli for valuable technical help and Epitech Italia for partly supporting this study.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sofia Magina
    • 1
    • 2
    • 3
    Email author
  • Carina Esteves-Pinto
    • 1
  • Eduardo Moura
    • 1
    • 2
  • Maria Paula Serrão
    • 1
  • Daniel Moura
    • 1
  • Stefania Petrosino
    • 4
  • Vincenzo Di Marzo
    • 4
  • Maria Augusta Vieira-Coelho
    • 1
    • 2
  1. 1.Institute of Pharmacology and Therapeutics, Faculty of MedicineUniversity of PortoPortoPortugal
  2. 2.Institute for Molecular and Cell BiologyUniversity of PortoPortoPortugal
  3. 3.Department of Dermatology and VenereologyH. S. JoãoPortoPortugal
  4. 4.Endocannabinoid Research Group, Institute of Biomolecular ChemistryConsiglio Nazionale delle RicerchePozzuoliItaly

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