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Organogold drug Auranofin exhibits anti-melanogenic activity in B16F10 and MNT-1 melanoma cells

  • Shilpi GoenkaEmail author
  • Sanford R. Simon
Concise Communication
  • 19 Downloads

Abstract

Auranofin (AF) is an organogold FDA-approved drug for treating rheumatism and has been repurposed for several pharmacological applications based on its anti-bacterial, anti-fungal and anti-inflammatory activities. To the best of our knowledge, there has been no study on effects of AF on melanogenesis yet. Hence, in this work, we studied the effect of AF on melanogenesis using B16F10 mouse melanoma cells and validated results in MNT-1 human melanoma cells. Melanogenesis assay was conducted with concentrations of AF determined to be nontoxic in B16F10 cells as well as HaCaT human epidermal cell line for a duration of 48 h, followed by various assays to delineate mechanisms of melanogenesis inhibition. Ultrastructural analysis was conducted to study further if AF affected melanosome maturation and protein levels of a key melanogenic protein, tyrosinase, and the maturation signaling molecule, cyclic adenosine monophosphate (cAMP), was estimated. Our results demonstrate that AF at nontoxic concentrations of 0.25–1 µM significantly inhibited melanin synthesis in a dose-dependent manner with significant inhibition of 32.85% at 1 µM. The study of mechanisms of melanogenesis inhibition revealed that AF inhibited tyrosinase activity in lysates of B16F10 cells but did not show a direct effect on purified mushroom tyrosinase activity or on copper chelation in a cell-free system, nor did it affect levels of B16F10 tyrosinase protein levels. However, AF significantly down-regulated cAMP levels, inhibited cellular ROS and increased number of melanosomes in immature stages, and also exhibited anti-melanogenic activity in B16F10–HaCaT cocultures. Furthermore, AF showed anti-melanogenic efficacy in MNT-1 cell monocultures and cocultures with an inhibition of intracellular tyrosinase activity. In summary, our results demonstrate a proof-of-principle for AF as a depigmenting agent for hyperpigmentation disorders and adjuvant for melanoma therapeutics.

Keywords

Auranofin Drug repurposing Anti-melanogenic Tyrosinase Melanosome maturation 

Abbreviations

AF

Auranofin

KA

Kojic acid

DMEM

Dulbecco’s modified Eagle’s medium

HI-FBS

Heat-inactivated fetal bovine serum

ROS

Reactive oxygen species

LDH

Lactate dehydrogenase

MEM

Minimum essential medium

ELISA

Enzyme-linked immunosorbent assay

cAMP

Cyclic adenosine monophosphate

L-DOPA

3,4-Dihydroxy-l-phenylalanine

PV

Pyrocatechol violet

Notes

Acknowledgements

We would like to thank Susan Van Horn for help with TEM sample preparation and imaging and Dr. Michael Marks, University of Pennsylvania for gracious gift of MNT-1 human melanoma cells. This study did not receive any funding in the public, commercial, or not-for-profit sectors.

Author contributions

SG conceptualized, designed and performed the experiments, analyzed the data,  wrote the manuscript and critically revised the manuscript. SRS provided funding for supplies and reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Human or animal rights statement

This article does not contain any studies involving animals or human participants.

Supplementary material

403_2019_1974_MOESM1_ESM.docx (463 kb)
Supplementary file1 (DOCX 463 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringStony Brook UniversityStony BrookUSA
  2. 2.Department of PathologyStony Brook UniversityStony BrookUSA
  3. 3.Department of Biochemistry and Cellular BiologyStony Brook UniversityStony BrookUSA

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