期刊
PHARMACEUTICALS
卷 12, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/ph12020085
关键词
xanthones; melanoma; macrophages; cytokines
资金
- FCT/MCTES-Foundation for Science and Technology, I.P.
- European Regional Development Fund (ERDF) through the COMPETE-Programa Operacional Factores de Competitividade (POFC) programme [UID/Multi/04423/2013, UID/Multi/04423/2019, UID/Multi/04546/2013, UID/Multi/04546/2019, PTDC/MAR-BIO/4694/2014, POCI-01-0145-FEDER-016790, 3599-PPCDT]
- Fundação para a Ciência e a Tecnologia [UID/Multi/04546/2013] Funding Source: FCT
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 (GI(50)) = 55.0 +/- 2.3 mu M), 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-1 beta (IL-1 beta) and interleukin-10 (IL-10), but stimulated tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) 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.
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