Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells

Kong, Jin; Li, Shanshan; Ma, Qi; Liu, Lei; Zheng, Liang‐Wen

doi:10.1111/and.13280

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…Ge Xu et al revealed that the down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA via proteomics analysis [31]. In addition, Jin Kong et al demonstrated through experiments that DHA could inhibit the expression of HSP70 and induce apoptosis in PC3 cells [32]. Furthermore, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ) [33].…”

Section: Induction Of Apoptosismentioning

confidence: 99%

Dihydroartemisinin: A Potential Natural Anticancer Drug

Dai¹,

Zhang²,

Chen³

et al. 2021

Int. J. Biol. Sci.

132

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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: Induction Of Apoptosismentioning

confidence: 99%

Dihydroartemisinin: A Potential Natural Anticancer Drug

Dai¹,

Zhang²,

Chen³

et al. 2021

Int. J. Biol. Sci.

132

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“…Malignant tumors threaten the life safety of people all over the world and have become the main cause of death together with cardiovascular and cerebrovascular diseases and respiratory diseases (115). It has been demonstrated that DHA exerts significant anti-tumor activity in a variety of malignant tumors, and it has no toxicity to normal cells at appropriate doses (18,20,85,94,116,117). It has been found that DHA not only is used as an adjuvant drug in combination with other chemotherapy drugs to improve drug resistance and enhance tumor killing function, but also has a significant inhibitory effect on tumors (21,29,34,39,45,46,70).…”

Section: The Anti-tumor Activity Of Dhamentioning

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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“…Heat shock proteins are a family of molecular chaperones involved in protein folding and are induced by heat shock or other stressors [18]. Both HSP27 and HSP70 play signi cant roles in cancer development and metastasis by inhibition of apoptosis [19,20]. The reduction of HSP27 and HSP70 further implies that DHA triggers apoptosis by blocking the anti-apoptotic targets.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Exhibits Antitumor Activity Toward Human Gastric Cancer Cells Through the Endoplasmic Reticulum Stress Pathway

Chen

Wang

Chen

et al. 2021

Preprint

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Background: Gastric cancer is the most fatal digestive tract tumor. The current treatment of gastric cancer often causes adverse effects. Dihydroartemisinin (DHA), a first-line antimalarial drug, is a derivative of a compound from a well-known Chinese medicinal plant Artemisia annua. DHA demonstrates antitumor activities toward many different types of cancer while exerts no apparent adverse effects on normal cells, making it a promising lead compound for cancer treatment. DHA induces apoptosis in Gastric cancer cell line 7901 (SGC-7901). However, the exact mechanism of this antitumor activity remains not fully explored. Methods: A CCK-8 assay to detect cell viability with DHA treatment in gastric cancer SGC-7901. The colony formation was visualized by crystal violet staining. The DHA-treatment cells were stained by Annexin-V FITC/PI dye and then subject to cell flow cytometry. The apoptosis was further observed in the Hoechst staining assay. Real-time qPCR was conducted to detect apoptosis-related markers. Western blotting was conducted to detect the protein levels of the endoplasmic reticulum (ER) stress pathway-related proteins. KIRA6, an ER stress pathway inhibitor was applied to find out whether it could reverse the cell death. Results: DHA induced dose-dependent apoptosis in Gastric SGC-7901 cell with an IC50 of about 4 mg/ mL. It significantly increased the proportion of apoptotic cells in a dose-dependent pattern in the Annexin V/PI flow cytometry. Significantly higher percentages of cells with a more prominently stained nucleus were observed in the Hoechst staining assay. In qPCR assay, the mRNA level of Bcl-2 was significantly decreased while that of Bax was significantly increased in a dose-dependent manner after DHA treatment. In the western blot assay, increased Bax and Bim and decreased Caspase 9, Bcl-2 were observed. Consistently, the levels of pro-apoptotic proteins were increased while those of anti-apoptotic ones were decreased as shown in the Human Apoptosis Array assay after DHA treatment. DHA stimulated the expression of GRP78, ATF4, IRE1, CHOP, and phosphorylated c-Jun (p-c-Jun) as revealed in western blotting. The cell death caused by DHA treatment was reversed by KIRA6. Conclusions: DHA exerts its antitumor activity on SGC-7901 cells through the IRE1/c-Jun ER stress pathway.

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Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells

Cited by 12 publications

References 32 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 Exhibits Antitumor Activity Toward Human Gastric Cancer Cells Through the Endoplasmic Reticulum Stress Pathway

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