Huaier Granule extract inhibit the proliferation and metastasis of lung cancer cells through down-regulation of MTDH, JAK2/STAT3 and MAPK signaling pathways

Yang, Chong‐Ren; Wu, Huan; Wang, Xinheng; Wang, Chenyang; Gan, Lei; Zhu, Jie; Tong, Jiabing; Li, Zegeng

doi:10.1016/j.biopha.2018.02.028

Cited by 42 publications

(37 citation statements)

References 25 publications

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“…12 Upregulation of TRIM32 correlated with enhanced cell proliferation and poor prognosis in hepatocellular carcinoma. 17,18 In this study, we demonstrate that TRIM32 is overexpressed in lung cancer tissues and cell lines. 14 Janus kinases (JAKs)/signal transducer and activator of transcriptions (STATs) is an important pathway to regulate multiple gene expression and biological behavior in cells.…”

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confidence: 50%

Expression and the potential functions of TRIM32 in lung cancer tumorigenesis

Yin

Chen

2018

J of Cellular Biochemistry

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TRIM32 is a member of the tripartite motif (TRIM) family, which has been associated with tumorigenesis. However, its expression and potential functional role(s) in lung cancer progression have not been fully understood. To evaluate the relationship between the expression of TRIM32 and the prognosis of patients with lung cancer, an independent data set (The Human Protein Atlas website) was introduced. The expression and function analysis of TRIM32 in lung cancer cell lines were also performed by using cell counting kit‐8, flow cytometry, transwell, real‐time polymerase chain reaction and Western blot analysis. Our data showed that TRIM32 was overexpressed in lung cancer tissues and cell lines and was associated with a poor prognosis. TRIM32 silencing inhibited cell proliferation, migration, invasion, adhesion, and the activation of janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. The results showed knockdown of TRIM32 in NCI‐H446 cells also inhibited cell growth in nude mice in the xenograft model. Additionally, TRIM32 overexpression promoted lung cancer cell proliferation and motility and mediated the expression of Bax, Bcl‐2, cleaved caspase‐3, matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 were inhibited by JAK2/STAT3 signaling inhibitor (AG490). Taken together, our findings suggest that TRIM32 may regulate lung cancer cell proliferation, apoptosis, and motility through activating the JAK2/STAT3‐signaling pathway and may be a novel and promising target for lung cancer.

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confidence: 50%

Expression and the potential functions of TRIM32 in lung cancer tumorigenesis

Yin

Chen

2018

J of Cellular Biochemistry

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“…In recent years, the anti-cancer effect of Huaier has aroused widespread interest, including its anti-proliferation, apoptosis-promoting, autophagy-enhancing, and anti-metastasis effects through many signal pathways. Chen et al [2] demonstrated that Huaier inhibits angiogenesis via suppressing JAK2/STAT3 and MAPK signaling pathways in lung cancer cells. Wang et al [12] suggested that Huaier induces autophagy by regulating the mTOR/S6K pathway in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…In recent decades, Huaier has gained growing popularity due to its newly discovered property as an adjuvant therapy for cancer. Many studies have proved the inhibitory effects of Huaier in some cancer cell lines, such as breast cancer [1], lung cancer [2], and gastric cancer [3]. Huaier is also able to increase the sensitivity of tumor cells to chemotherapy and radiotherapy [4,5].…”

Section: Introductionmentioning

confidence: 99%

The Anticancer Effect of Huaier Extract in Renal Cancer 786-O Cells

Wei

Liu

et al. 2018

Pharmacology

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Background: Trametes robiniophila Murr (Huaier) has been used as an adjuvant therapy of tumor in traditional Chinese medicine for many years, but the underlying mechanisms are largely unknown. In the present study, we tested the inhibitory effect of Huaier extract on renal cancer 786-O cells and explored the possible mechanisms. Methods: 786-O cells were treated by gradient concentrations of Huaier extract, cell viability, invasion, migration and apoptosis were assessed by cell counting kit 8, cell scratch, transwell, and flow cytometry assay in vitro. The changes in protein level were detected by western blot analysis. Finally, the anticancer effect of Huaier was tested in vivo by nude mouse tumorigenicity assay. Results: Viability of 786-O cells was suppressed by Huaier in a time- and dose-dependent manner; cell invasion and migration were also dramatically inhibited. Flow cytometry assays showed that Huaier could induce cell apoptosis. Western blotting analysis indicated that Huaier suppressed the activation of PI3K/AKT/mTOR/p70S6K/4E-BP1 signaling pathway. We also found that Huaier could partly reverse the epithelialmesenchymal transition (EMT) process. In vivo experiment indicated that tumor growth in the xenograft mouse model was suppressed by Huaier. Conclusion: Huaier plays an anticancer effect partially through the suppression of the PI3K/AKT/mTOR/p70S6K/4E-BP1 pathway and by reversing the EMT process. Huaier may act as an effective agent for treating renal cell carcinoma.

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“…MAPKs include three major subfamilies, namely ERKs, JNKs, and p38 MAPK, that contribute to the control of cancer development and progression [30][31][32][33]. Huaier Granule extract suppresses proliferation and metastasis in lung cancer cells by downregulating the MTDH, JAK2/STAT3, and MAPK signalling pathways [34]. MAPK inhibitors, particularly JNK, enhance the cell death effects in H 2 O 2 -treated lung cancer cells by increasing superoxide anion and glutathione depletion [35].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non–Small Cell Lung Cancer through Inactivating ERK/CTSD Signalling Pathways

et al. 2020

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Praeruptorin C (PC) reportedly has beneficial effects in terms of antiinflammation, antihypertension, and antiplatelet aggregation, and it potentially has anticancer activity. However, the effect of PC on human non–small cell lung cancer (NSCLC) is largely unknown. Compared with the effects of praeruptorin A and praeruptorin B, we observed that PC significantly suppressed cell proliferation, colony formation, wound closure, and migration and invasion of NSCLC cells. It induced cell cycle arrest in the G0/G1 phase, downregulated cyclin D1 protein, and upregulated p21 protein. PC also significantly reduced the expression of cathepsin D (CTSD). In addition, the phosphorylation/activation of the ERK1/2 signalling pathway was significantly suppressed in PC-treated NSCLC cells. Cotreatment with PC and U0126 synergistically inhibited CTSD expression, cell migration, and cell invasion, which suggests that the ERK1/2 signalling pathway is involved in the downregulation of CTSD expression and invasion activity of NSCLC cells by PC. These findings are the first to demonstrate the inhibitory effects of PC in NSCLC progression. Therefore, PC may represent a novel strategy for treating NSCLC.

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Huaier Granule extract inhibit the proliferation and metastasis of lung cancer cells through down-regulation of MTDH, JAK2/STAT3 and MAPK signaling pathways

Cited by 42 publications

References 25 publications

Expression and the potential functions of TRIM32 in lung cancer tumorigenesis

Expression and the potential functions of TRIM32 in lung cancer tumorigenesis

The Anticancer Effect of Huaier Extract in Renal Cancer 786-O Cells

Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non–Small Cell Lung Cancer through Inactivating ERK/CTSD Signalling Pathways

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