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1,2-Dihydroxyxanthone: Effect on A375-C5 Melanoma Cell Growth Associated with Interference with THP-1 Human Macrophage Activity

1
ICBAS, Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
2
FP-ENAS Research Unit, UFP Energy, Environment and Health Research Unit, CEBIMED, Biomedical Research Center, Fernando Pessoa University, Praça 9 de Abril, 349, 4249-004 Porto, Portugal
3
LAQV/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
4
Molecular Oncology and Viral Pathology GRP - IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
5
LPCC, Research Department - Portuguese League Against Cancer (LPPC - NRN), Estrada Interior da Circunvalação, 6657, 4200-172 Porto, Portugal
6
i3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
7
IBMC, Institute for Molecular and Cell Biology, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
8
CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
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Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(2), 85; https://doi.org/10.3390/ph12020085
Received: 30 April 2019 / Revised: 1 June 2019 / Accepted: 3 June 2019 / Published: 4 June 2019
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Abstract

Xanthones have been suggested as prospective candidates for cancer treatment. 1,2- dihydroxyxanthone (1,2-DHX) is known to interfere with the growth of several cancer cell lines. We investigated the effects of 1,2-DHX on the growth of the A375-C5 melanoma cell line and THP-1 human macrophage activity. 1,2-DHX showed a moderate growth inhibition of A375-C5 melanoma cells (concentration that causes a 50% inhibition of cell growth (GI50) = 55.0 ± 2.3 µM), but strongly interfered with THP-1 human macrophage activity. Supernatants from lipopolysaccharide (LPS)-stimulated THP-1 macrophage cultures exposed to 1,2-DHX significantly increased growth inhibition of A375-C5 cells, when compared to supernatants from untreated LPS-stimulated macrophages or to direct treatment with 1,2-DHX only. 1,2-DHX decreased THP-1 secretion of interleukin-1β (IL-1β) and interleukin-10 (IL-10), but stimulated tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) production. This xanthone also inhibited nitric oxide (NO) production by RAW 264.7 murine macrophages, possibly through inhibition of inducible NO synthase production. In conclusion, these findings suggest a potential impact of 1,2-DHX in melanoma treatment, not only due to a direct effect on cancer cells but also by modulation of macrophage activity. View Full-Text
Keywords: xanthones; melanoma; macrophages; cytokines xanthones; melanoma; macrophages; cytokines
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MDPI and ACS Style

Silva, V.; Cerqueira, F.; Nazareth, N.; Medeiros, R.; Sarmento, A.; Sousa, E.; Pinto, M. 1,2-Dihydroxyxanthone: Effect on A375-C5 Melanoma Cell Growth Associated with Interference with THP-1 Human Macrophage Activity. Pharmaceuticals 2019, 12, 85.

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