Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity

Yang, Ke; Bao, Tianhao; Wu, Xuesong; Tang, Haoran; Wang, Yan; Ge, Jiayun; Fu, Bimang; Xu, Meng; Chen, Li; Zhang, Cheng; Tan, Yuqi; Chen, Haotian; Guo, Zhitang; Fan, Ni; Lei, Xuefen; Shi, Zhitian; Wei, Dong; Wang, Lin

doi:10.1016/j.bbrc.2016.12.114

Cited by 56 publications

(39 citation statements)

References 28 publications

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“…23 Deng et al showed that SCU inhibits human renal cancer cell proliferation and migration via upregulation of phosphatase and tensin homolog, 24 while Ke et al reported that SCU effectively inhibits hepatocellular carcinoma metastasis in vivo and the migration and invasion of hepatocellular carcinoma cells in vitro. 21 Other researchers have reported that SCU induces apoptosis and G2/M arrest, inhibits cell proliferation of prostate cancer PC3 cells, and sensitizes the cells to chemotherapy. 16 In this study, we first investigated the toxicity of SCU to A549 lung adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…SCU exhibits activity against several cancer cells. 20,21 Sun et al reported that SCU enhanced cisplatin-induces apoptosis and autophagy via the extracellular signal-regulated kinase (ERK)/P53 or c-met/AKT signaling pathways. 22 This group also revealed that SCU induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT signaling pathways in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

Cao

Liu

et al. 2019

Thoracic Cancer

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Background Scutellarin (SCU), a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.‐Mazz., increases autophagy and apoptosis in the adenocarcinoma A549 cell line, which is resistant to cisplatin. However, whether SCU alone has antitumor activity against non‐small cell lung cancer (NSCLC) is unknown. Methods Cell Counting Kit‐8, flow cytometry, colony formation, Hoechst 33258 staining, and Western blot analyses were used to examine the proliferation and apoptosis of A549 cells treated with SCU and the possible molecular mechanisms. Results The cell viability assay indicated that SCU markedly suppressed the proliferation of A549 cells in concentration and time‐dependent manners. SCU caused significant G0/G1 phase arrest and apoptosis, as evidenced by flow cytometric analyses, Hoechst 33258 staining, and Western blot analyses of cyclin D1, cyclin E, BCL‐2, cleaved‐caspase‐3, and BAX. Furthermore, SCU treatment reduced the level of pan‐AKT, phosphorylated (p)‐mTOR, mTOR, BCL‐XL, STAT3, and p‐STAT3, and increased the level of 4EBP1. Conclusions SCU can suppress proliferation and promote apoptosis in A549 cells through AKT/mTOR/4EBP1 and STAT3 pathways. This suggests that SCU may be developed into a promising antitumor agent for treating NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

Cao

Liu

et al. 2019

Thoracic Cancer

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“…These suggest that independent mechanisms related to HCC progression may regulate Dlg5 and Girdin expression, respectively. Full‐length Girdin expression is downregulated by an alternatively splicing event in the early stage of tumor progression, and can be upregulated by STAT3 activation in the late stage of tumor progression . Dlg5 expression can be downregulated by TGF‐β1, which is elevated in HCC patients, particularly with aggressive and metastatic HCC .…”

Section: Discussionmentioning

confidence: 99%

Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5

Yang

Bao

Zhou

et al. 2017

Intl Journal of Cancer

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Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent nontumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients. Dlg5-silencing promoted epithelial-mesenchymal transition, invadopodium formation, gelatin degradation function, and invadopodium-associated invasion of HepG2 cells. In contrast, Dlg5 overexpression inhibited epithelial-mesenchymal transition, functional invadopodium formation, and invasion of SK-Hep1 cells. Both Girdin and Tks5, but not the Tks5 nonphosphorylatable mutant, were responsible for the enhanced invadopodium formation and invasion of Dlg5-silenced HepG2 cells. Furthermore, Dlg5 interacted with Girdin and interfered with the interaction of Girdin and Tks5. Dlg5 silencing promoted Girdin and Tks5 phosphorylation, which was abrogated by Girdin silencing and rescued by inducing shRNA-resistant Girdin expression. Moreover, Dlg5 overexpression significantly inhibited HCC intrahepatic and lung metastasis in vivo. Taken together, our data indicate that Dlg5 acts as a novel regulator of invadopodium-associated invasion via Girdin and by interfering with the interaction between Girdin and Tks5, which might be important for Tks5 phosphorylation in HCC cells. Conceivably, Dlg5 may act as a new biomarker for prognosis of HCC patients.

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“…ISL increases PTEN expression by decreasing miR-374a expression, thereby inhibiting AKT signaling in breast cancer therapies (82)(83)(84). Scutellarin is an active flavonoid from Erigeron breviscapine and blocked the migration and invasion of HepG2 cells by inhibiting the STAT3/girdin/ AKT axis (85). Resveratrol (RES) is found in grapes, berries, and peanuts and inhibited activation of multiple survival pathways, including the PI3K/AKT pathway, thereby inducing cancer cell apoptosis (86,87).…”

Section: Natural Compoundsmentioning

confidence: 99%

AKT as a Therapeutic Target for Cancer

et al. 2019

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Many cellular processes in cancer are attributed to kinase signaling networks. V-akt murine thymoma viral oncogene homolog (AKT) plays a major role in the PI3K/AKT signaling pathways. AKT is activated by PI3K or phosphoinositidedependent kinases (PDK) as well as growth factors, inflammation, and DNA damage. Signal transduction occurs through downstream effectors such as mTOR, glycogen synthase kinase 3 beta (GSK3b), or forkhead box protein O1 (FOXO1). The abnormal overexpression or activation of AKT has been observed in many cancers, including ovarian, lung, and pancreatic cancers, and is associated with increased cancer cell proliferation and survival. Therefore, targeting AKT could provide an important approach for cancer prevention and therapy. In this review, we discuss the rationale for targeting AKT and also provide details regarding synthetic and natural AKT-targeting compounds and their associated studies.

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Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity

Cited by 56 publications

References 28 publications

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5

AKT as a Therapeutic Target for Cancer

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