Artesunate enhances γδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells

Peng, Qian; Yong-wen, Zhang; Zhou, Zhonghai; Liu, Junquan; Yue, Su-Yang; Guo, Xiao; Sun, Li-Ying; Lv, Xiaoting; Chen, Jian-Qun

doi:10.1080/08923973.2017.1386212

Cited by 26 publications

(24 citation statements)

References 42 publications

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“…Immunomodulation also plays a vital role in artesunate-mediated anti-cancer effects [671,674,691,692]. Artesunate induces Th1 differentiation into CD4 + T cells to mediate apoptosis in murine ovarian cancer ID8 cells [674].…”

Section: Artesunatementioning

confidence: 99%

“…Besides, artesunate also exerts immunosuppression through forkhead box P3 (Foxp3) down-regulation in T cells and decreases prostaglandin E 2 (PGE 2 ) production in human cervical cancer Caski and HeLa cells [671]. Moreover, it enhances γδ T cell-mediated anti-cancer effect through augmenting γδ T cell cytotoxicity and decreasing TGF-β1 levels to reverse immune escape in human hepatocellular carcinoma HepG2 cells [692].…”

Section: Artesunatementioning

confidence: 99%

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Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Artesunatementioning

confidence: 99%

Section: Artesunatementioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…The enhanced DTH response was also observed in dihydroartemisinin‐treated BALB/c mice against sheep red blood cells 163 . γδ T cells play an important role in the antitumor activity of dihydroartemisinin and artesunate against pancreatic cancer cells (SW1990, BxPC‐3, and PANC‐1) and liver cancer cells (HepG2), respectively 164,165 . Mechanistically, dihydroartemisinin increased the expression of intracellular perforin, granulase B, and the production of IFN‐γ, and then enhanced the γδ T cell‐mediated killing activity 164 .…”

Section: Molecular Mechanisms On Natural Products In Tumor Immunotherapymentioning

confidence: 83%

“…Mechanistically, dihydroartemisinin increased the expression of intracellular perforin, granulase B, and the production of IFN‐γ, and then enhanced the γδ T cell‐mediated killing activity 164 . In contrast, elevating the expression of GraB and Fas, as well as reducing the secretion of TGFβ1, may be important artesunate mechanisms promoting the antitumor activity of γδ T cells 165 . Furthermore, artemisinin enhanced the antitumor immune response in 4T1 breast cancer cells in vivo by promoting T cell function and quelling immunosuppression from Tregs and MDSCs in the tumor 78 .…”

Section: Molecular Mechanisms On Natural Products In Tumor Immunotherapymentioning

confidence: 99%

Natural products and their derivatives: Promising modulators of tumor immunotherapy

Deng

et al. 2020

Journal of Leukocyte Biology

138

104

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A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid-derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF-B, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.

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“…Furthermore, human γδ T cells can induce the death of HCC cell lines and reverse the immune escape of HCC in vitro ( 47 ). Moreover, the anti-HCC function of peripheral γδ T cells, especially Vγ9Vδ2 T cells, can be further enhanced by activating agents, including histone deacetylase inhibitors ( 48 ), pyrophosphate ( 49 ), zoledronate ( 20 ), CD226 ( 50 ), and even the Chinese herb artesunate ( 51 ).…”

Section: Role Of γδ T Cells In Liver Cirrhosis and Hccmentioning

confidence: 99%

Diverse Functions of γδ T Cells in the Progression of Hepatitis B Virus and Hepatitis C Virus Infection

Hou

2021

Front. Immunol.

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are primary risk factors for a wide spectrum of liver diseases that severely affect human health. The liver is an immunological organ that has an abundance of immune cells. Thus, various innate or adaptive immune cells are involved in the progression of HBV or HCV infection. Among those cells, a unique kind of immune cell, the γδ T cell, contributes to promoting or inhibiting the progression of liver diseases. To reveal the diverse roles of γδ T cells in HBV or HCV infection, the properties and functions of these cells in human and mouse models are analyzed. Here, we briefly describe the characteristics and functions of γδ T cells subsets in liver diseases. Then, we fully discuss the diverse roles of γδ T cells in the progression of HBV or HCV infection, including stages of acute infection, chronic infection, liver cirrhosis, and hepatocellular carcinoma. Finally, the functions and existing problems of γδ T cells in HBV or HCV infection are summarized. A better understanding of the function of γδ T cells during the progression of HBV and HCV infection will be helpful for the treatment of virus infection.

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Artesunate enhances γδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells

Abstract: Artesunate has several mechanisms for augmenting the antitumor immune responses mediated by γδ T cells. These results suggested artesunate may be an efficacious agent in the treatment of hepatocellular carcinoma.

Cited by 26 publications

References 42 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Natural products and their derivatives: Promising modulators of tumor immunotherapy

Diverse Functions of γδ T Cells in the Progression of Hepatitis B Virus and Hepatitis C Virus Infection

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