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-g + 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 + Tcells were normalized by DHA treatment. DHA diminished expression of IL-10 and IL-6, and increased the expression of IFN-g 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.

Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism.Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo.Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role.Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8+CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8+CTLs. Moreover, DHA impacts STAT3-induced EMT and MMPS in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma in vitro and in vivo. These results have important implications for the potential use of DHA in the treatment of melanoma in humans.