A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

Chen, Yonglin; Shi, Songshan; Wang, Huijun; Li, Ning; Su, Juan; Chou, Gui‐Xin; Wang, Shunchun

doi:10.3390/ijms17071015

Cited by 17 publications

(9 citation statements)

References 62 publications

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“…Hsp90 is generally overexpressed in OS and promotes tumour progression through the stabilization of its oncogenic client proteins (Chen et al, 2016; Sottile & Nadin, 2018). Based on the results described above, zey significantly altered the expression of Hsp90 client proteins, such as Chk1, CyclinD, and p53.…”

Section: Resultsmentioning

confidence: 99%

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Yang

Xiao

Sun

et al. 2021

Phytotherapy Research

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A safer and more effective combination strategy designed to enhance the efficacy and minimize the toxicity of cisplatin in osteosarcoma (OS) is urgently needed. Zeylenone (zey), a cyclohexene oxide compound, exerted an obvious inhibitory effect on several cancer cell lines and exhibited little cytotoxicity towards normal cells, enabling zey to play a unique role in combination therapy. Thus, the study aimed to determine whether the combination of zey and cisplatin produces synergistic antitumour effects on OS and to further explore molecular mechanisms. Initially, we found that zey potentiated the anti-osteosarcoma efficacy of cisplatin and exhibited synergistic interactions with cisplatin in vitro, which also were confirmed in vivo by using xenograft model. Mechanistically, zey and cisplatin synergistically induced DNA damage, cell cycle arrest, necrosis, and apoptosis in OS cells. Importantly, zey had a high binding affinity for Hsp90 and reduced the expression of Hsp90, which further induced the suppression of AKT/GSK3β signalling axis and the degradation of Fanconi anaemia (FA) pathway proteins. Thus, the Hsp90/AKT/GSK3β and FA pathway are the key to the synergism between zey and cisplatin. Overall, zey shows promise for development as a cisplatin chemosensitizer with clinical utility in restoring cisplatin sensitivity of cancer cells.

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Section: Resultsmentioning

confidence: 99%

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Yang

Xiao

Sun

et al. 2021

Phytotherapy Research

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“…Pro- or anti-apoptotic proteins and caspases that regulate apoptosis have been observed in several suicide system treatments ( 27 ). overall, the pro-apoptotic proteins Bax, cleaved caspase-3 or -9 were upregulated the and anti-apoptotic protein, Bcl-2 was downregulated when suicide systems were implemented ( 28 ). Strong expression of both caspase-3 and Bcl-2 in responses to the suicide system suggests that pathways involving caspases and the Bcl-2 family may be active in these systems ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of a dual-specific lentiviral vector carrying the Escherichia coli purine nucleoside phosphorylase gene

Wang

Sun

et al. 2017

International Journal of Oncology

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The Escherichia coli purine nucleoside phosphorylase/Fludarabine phosphate (ePNP/Fludara) suicide system has several drawbacks, such as side-effects and the low efficiency of ePNP expression. In this study, we evaluated the antitumor effects of the dual-specific 8HSEs-hTERTp-ePNP/Fludara suicide system under hyperthermia in vitro and in vivo. Luciferase activities from the 8HSEs-hTERT and CMV promoters were compared using the dual luciferase assay in SW480 (high hTERT expression) and MKN74 cells (hTERT-negative) in the presence and absence of hyperthermia. Then, we investigated the effects of overexpressing the suicide gene ePNP using 8HSEs-hTERT-driven lentiviral vectors with Fludara on in vitro cell viability, side-effects, apoptosis, cycle distribution, colony formation and in vivo xenograft tumor growth. At 43°C, luciferase activity from the 8HSEs-hTERT promoter was significantly increased in SW480 cells, but not in MKN74 cells. Importantly, luciferase activities from the 8HSEs-hTERT promoter were much higher than from the CMV promoter in hTERT-expressing SW480 cells under heated conditions. The in vitro quantitative analysis showed a 4-fold higher ePNP protein expression from the 8HSEs-hTERT promoter at 43°C than at 37°C in SW480 cells and the ePNP mRNA expression in SW480 cells at 43°C was also higher than at 37°C. Conversely, ePNP mRNA and protein expression were low, almost absent, in hTERT-negative MKN74 cells with or without hyperthermia. After Fludara addition, cell cytotoxicity assays showed that the significant inhibitory effect of the 8HSEs-hTERTp-ePNP on SW480 cells was dose- and time-dependent with hyperthermia. The 8HSEs-hTERTp-ePNP/Fludara suicide system significantly inhibited SW480 cell viability, colony formation, cell cycle progression and induced apoptosis in vitro, but also induced significant bystander effects, especially under the heated conditions. At the protein level, the suicide system significantly promoted Bax, caspase-3 and p53 expression and suppressed Bcl-2 expression. In sections from mouse xenografts, TUNEL assays showed that the suicide system reduced xenograft growth and induced SW480 apoptosis. These results indicated that the combinatorial cancer- and heat-specific promoter system has great potential for improving the efficacy of cancer treatment with hyperthermia. The 8HSEs-hTERTp-ePNP/Fludara system may serve as a powerful strategy for cancer gene therapy combined with hyperthermia.

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“…Synergistic application of triptolide and celastrol can mitigate effect of increased HSP27 and HSP70, inhibit growth of cancer cells, and induce apoptosis in cancer cells ( Jiang et al, 2015 ). Homogeneous polysaccharide-0-1 (SCP-0-1) from Schisandra chinensis induces mitochondrial apoptosis in human hepatocellular liver carcinoma, a mechanism involved in the downregulation of HSP90 and inhibition of Akt pathway ( Chen et al, 2016 ). Patrinia heterophylla , a member of Valerianaceae family, inhibits expression of HSP90α to induce apoptosis in leukemia K562 cells ( Wei et al, 2012 ).…”

Section: Tcm Regulates Expression Of Hspsmentioning

confidence: 99%

Traditional Chinese Medicine Targeting Heat Shock Proteins as Therapeutic Strategy for Heart Failure

Wang

et al. 2022

Front. Pharmacol.

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Heart failure (HF) is the terminal stage of multifarious heart diseases and is responsible for high hospitalization rates and mortality. Pathophysiological mechanisms of HF include cardiac hypertrophy, remodeling and fibrosis resulting from cell death, inflammation and oxidative stress. Heat shock proteins (HSPs) can ameliorate folding of proteins, maintain protein structure and stability upon stress, protect the heart from cardiac dysfunction and ameliorate apoptosis. Traditional Chinese medicine (TCM) regulates expression of HSPs and has beneficial therapeutic effect in HF. In this review, we summarized the function of HSPs in HF and the role of TCM in regulating expression of HSPs. Studying the regulation of HSPs by TCM will provide novel ideas for the study of the mechanism and treatment of HF.

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A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

Cited by 17 publications

References 62 publications

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Antitumor effects of a dual-specific lentiviral vector carrying the Escherichia coli purine nucleoside phosphorylase gene

Traditional Chinese Medicine Targeting Heat Shock Proteins as Therapeutic Strategy for Heart Failure

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