Dihydroartemisinin inhibits melanoma by regulating CTL/Treg anti-tumor immunity and STAT3-mediated apoptosis via IL-10 dependent manner.

Abstract

BACKGROUND:

It has been shown that dihydroartemisinin (DHA) is effective in the treatment of malaria. Recently studies have demonstrated that DHA also regulates tumor cell growth, angiogenesis, T cell differentiation and generation. However, how DHA affects melanoma development remains poorly defined.

OBJECTIVES:

To investigate the effects of DHA on the proliferation and migration of melanoma in vivo and in vitro, and to explore its possible mechanism.

METHODS:

B16F10 cells and melanoma-bearing BALB/c mice were used to investigate the effects of DHA on melanoma.

RESULTS:

DHA had inhibitory effect on melanoma proliferation in a time-and dose-dependent manner. Treatment of DHA attenuated melanoma severity and histopathological changes in BALB/c mice. DHA also inhibited melanoma invasion, migration, and community formation in a dose-dependent manner. Flow cytometry revealed a significant increase in IFN-γ+CD8+ T cells in the DHA groups. In tumor microenvironment and spleen, DHA induced expansion of CD8+CTL, while, CD4+CD25+Foxp3+ regulatory T (Treg) cells and IL-10+CD4+CD25+ T cells were normalized by DHA treatment. DHA diminished expression of IL-10 and IL-6, and increased the expression of IFN-γ in the tumor and spleen. Moreover, DHA administration significantly promoted the mitochondrial apoptosis of melanoma by regulating the STAT3 pathway.

CONCLUSION:

DHA induces mitochondrial apoptosis and alters cytokines expression by inhibiting the phosphorylation of STAT3. DHA improves anti-tumor immunity in mice through controlling CD8+CTL function by counteracting IL-10-dependent Treg cells suppression, which promises to be an alternative drug for melanoma.

• Authors: Ran Yu, Linbo Jin, Fangfang Li, Manabu Fujimoto, Qiang Wei, Zhenhua Lin, Xiangshan Ren, Quanxin Jin, Honghua Li, Fanping Meng, Guihua Jin
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 99 Issue 3 Pg. 193-202 (Sep 2020) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 32859456 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Artemisinins
• IL10 protein, mouse
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Interleukin-10
• artenimol

Topics

• Administration, Oral
• Animals
• Apoptosis (drug effects, immunology)
• Artemisinins (pharmacology, therapeutic use)
• Cell Line, Tumor (transplantation)
• Drug Screening Assays, Antitumor
• Female
• Gene Expression Regulation, Neoplastic (drug effects, immunology)
• Humans
• Interleukin-10 (genetics, metabolism)
• Melanoma, Experimental (drug therapy, immunology, pathology)
• Mice
• Mitochondria (drug effects, pathology)
• Phosphorylation (drug effects, immunology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects, immunology)
• Skin Neoplasms (drug therapy, immunology, pathology)
• T-Lymphocytes, Cytotoxic (drug effects, immunology, metabolism)
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)
• Tumor Escape (drug effects, genetics)