Effects of Dihydroartemisinin, a Metabolite of Artemisinin, on Colon Cancer Chemoprevention and Adaptive Immune Regulation
| Autor: | Chun-Feng Zhang, Lina Chen, Lifei Hou, Zhi Liu, Cang-Hai Li, Daniel Henry Wang, Ting-Liang Jiang, Qi-Hui Zhang, Mallory Lager, Yun Luo, Chong-Zhi Wang, Chunping Wan, Chun-Su Yuan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Colorectal cancer
business.industry Metabolite medicine.medical_treatment Immune regulation Dihydroartemisinin Apoptosis General Medicine medicine.disease Chemoprevention Artemisinins chemistry.chemical_compound chemistry Colonic Neoplasms Genetics medicine Cancer research Humans Artemisinin business Molecular Biology medicine.drug |
| DOI: | 10.21203/rs.3.rs-744220/v1 |
| Popis: | Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention have not been systematically evaluated and compared, including on adaptive immune regulation. Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART. The anti-CRC potential of these compounds was compared using two different human CRC cell lines for cell cycle arrest, apoptotic induction, and anti-inflammation activities. Naive CD4+ T cells were also obtained for testing the compounds on the differentiation of Treg, Th1 and Th17. Using compound extraction and analytical methods, we observed for the first time that ART completely converted into its metabolites within 24 h, but no DHA was detected. Although ART did not obviously influence cancer cell growth in the concentration tested, DHA very significantly inhibited the cancer cell growth at relatively low concentrations. DHA included G2/M cell cycle arrest via upregulation of cyclin A and apoptosis. Both ART and DHA downregulated the pro-inflammatory cytokine expression. The DHA significantly promoted Treg cell proliferation, while both ART and DHA inhibited Th1 and Th17 cell differentiation. As a metabolite of ART, DHA possessed stronger anti-CRC activities. The DHA significantly inhibited cell growth via cell cycle arrest, apoptosis induction and anti-inflammation actions. The adaptive immune regulation is a related mechanism of actions for the observed effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|