Dihydroartemisinin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cell by Upregulating Tumor Necrosis Factor via JNK/NF-<i>κ</i>B Pathways

Wu, Long; Cheng, Yue; Deng, Junjian; Ye, Junjie

doi:10.1155/2019/9581327

Cited by 18 publications

(8 citation statements)

References 19 publications

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“…DHA also inhibited cell viability, migration, invasion and induced apoptosis of epithelial ovarian cancer (EOC) cells via inhibiting the hedgehog signaling pathway [48] (Figure 3). A recent study identified that DHA inhibited the growth and invasion of gastric cancer cells and confirmed that Cyclin D1-CDK4-Rb signaling played an important role in this process [49]. In addition, DHA could inhibit the proliferation, migration and invasion of MDA-MB-231 breast cancer cells with the AKT/steroid receptor coactivator (SRC) signaling pathway involved, thereby inhibiting breast tumor-induced osteolysis [50].…”

Section: Inhibition Of Metastasismentioning

confidence: 83%

Dihydroartemisinin: A Potential Natural Anticancer Drug

Dai¹,

Zhang²,

Chen³

et al. 2021

Int. J. Biol. Sci.

138

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Dihydroartemisinin (DHA) is an active metabolite of artemisinin and its derivatives (ARTs), and it is an effective clinical drug widely used to treat malaria. Recently, the anticancer activity of DHA has attracted increasing attention. Nevertheless, there is no systematic summary on the anticancer effects of DHA. Notably, studies have shown that DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stress. In this review, we comprehensively summarized the latest progress regarding the anticancer activities of DHA in cancer. Importantly, the underlying anticancer molecular mechanisms and pharmacological effects of DHA in vitro and in vivo are the focus of our attention. Interestingly, new methods to improve the solubility and bioavailability of DHA are discussed, which greatly enhance its anticancer efficacy. Remarkably, DHA has synergistic anti-tumor effects with a variety of clinical drugs, and preclinical and clinical studies provide stronger evidence of its anticancer potential. Moreover, this article also gives suggestions for further research on the anticancer effects of DHA. Thus, we hope to provide a strong theoretical support for DHA as an anticancer drug.

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Section: Inhibition Of Metastasismentioning

confidence: 83%

Dihydroartemisinin: A Potential Natural Anticancer Drug

Dai¹,

Zhang²,

Chen³

et al. 2021

Int. J. Biol. Sci.

138

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“…Hepatocellular carcinoma MHCC97-L cells are treated with DHA for Global gene expression profiles analysis. The results show that DHA regulates gene expression which is associated with angiogenesis, apoptosis, cell cycle and various pathways (64). As a kind of non-coding RNA, Micro-RNA (miR) plays an important role in tumor by connecting to mRNA to regulate gene expression (72) (58).…”

Section: Other Anti-tumor Effectsmentioning

confidence: 99%

Dihydroartemisinin: A Potential Drug for the Treatment of Malignancies and Inflammatory Diseases

Jin

Fujimoto

2021

Front. Oncol.

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Dihydroartemisinin (DHA) has been globally recognized for its efficacy and safety in the clinical treatment of malaria for decades. Recently, it has been found that DHA inhibits malignant tumor growth and regulates immune system function in addition to anti-malaria. In parasites and tumors, DHA causes severe oxidative stress by inducing excessive reactive oxygen species production. DHA also kills tumor cells by inducing programmed cell death, blocking cell cycle and enhancing anti-tumor immunity. In addition, DHA inhibits inflammation by reducing the inflammatory cells infiltration and suppressing the production of pro-inflammatory cytokines. Further, genomics, proteomics, metabolomics and network pharmacology of DHA therapy provide the basis for elucidating the pharmacological effects of DHA. This review provides a summary of the recent research progress of DHA in anti-tumor, inhibition of inflammatory diseases and the relevant pharmacological mechanisms. With further research of DHA, it is likely that DHA will become an alternative therapy in the clinical treatment of malignant tumors and inflammatory diseases.

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“…As an effective antimalarial substance, DHA has attracted widespread attention for its anticancer effect and low toxicity. Previous studies showed that DHA inhibited cell proliferation and induced apoptosis in human hepatocellular carcinoma cells by upregulating TNF expression via JNK/NF-κB pathways (Wu et al, 2019). Li et al demonstrates that DHA may repress esophageal FIGURE 6 | DHA suppresses the phosphorylation of mTOR S2448 , p70S6K T389 , p70S6K T421/S424 , and RPS6 S235/S236 in the LEG20 xenograft mice model, confirmed using IHC analysis.…”

Section: Discussionmentioning

confidence: 64%

“…Previous studies showed that DHA inhibited cell proliferation and induced apoptosis in human hepatocellular carcinoma cells by upregulating TNF expression via JNK/NF-κB pathways ( Wu et al, 2019 ). Li et al demonstrates that DHA may repress esophageal cancer glycolysis partly by down-regulating PKM2 (Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma Partially by Targeting AKT1 and p70S6K

et al. 2020

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Dihydroartemisinin (DHA), a sesquiterpene lactone with endoperoxide bridge, is one of the derivatives of artemisinin. In addition to having good antimalarial properties, DHA exhibits anticancer effects including against malignant solid tumors. However, the mechanism by which DHA inhibits the progression of esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is unclear. In this study, DHA was found to inhibit the proliferation of ESCC, and the underlying molecular mechanisms were explored. DHA inhibited ESCC cells proliferation and anchorage-independent growth. Flow cytometry analysis revealed that DHA significantly blocked cell cycle in the G1 phase. The results of human phospho-kinase array revealed that DHA downregulated the levels of p70S6KT389 and p70S6KT421/S424. Furthermore, the levels of mTORS2448, p70S6KT389, p70S6KT421/S424 and RPS6S235/S236 were decreased after DHA treatment in KYSE30 and KYSE150 cells. We then explored the proteins targeted by DHA to inhibit the mTOR-p70S6K-RPS6 pathway. Results of the in vitro kinase assay revealed that DHA significantly inhibited phosphorylation of mTORS2448 by binding to AKT1 and p70S6K kinases. In vivo, DHA inhibited the tumor growth of ESCC patient-derived xenografts and weakened p-mTOR, p-p70S6K, and p-RPS6 expression in tumor tissues. Altogether, our results indicate that DHA has antiproliferative effects in ESCC cells and can downregulate mTOR cascade pathway partially by binding to AKT1 and p70S6K. Thus, DHA has considerable potential for the prevention or treatment of ESCC.

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Dihydroartemisinin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cell by Upregulating Tumor Necrosis Factor via JNK/NF-κB Pathways

Cited by 18 publications

References 19 publications

Dihydroartemisinin: A Potential Natural Anticancer Drug

Dihydroartemisinin: A Potential Natural Anticancer Drug

Dihydroartemisinin: A Potential Drug for the Treatment of Malignancies and Inflammatory Diseases

Dihydroartemisinin Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma Partially by Targeting AKT1 and p70S6K

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