The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells

Zhang, Zhenxing; Liu, Ting; Yu, Man; Li, Kangdi; Li, Wenhua

doi:10.1186/s13046-018-0678-6

Cited by 58 publications

(41 citation statements)

References 39 publications

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“…33 Autophagy has been reported to play multiple roles in cell metastasis, especially in the establishment of a pre-metastatic niche. 36 Consistent with these studies, our findings indicated that XAG suppressed HCC cell metastasis by inducing autophagic cell death. 34 Similarly, fluvastatin inhibited bone metastasis of lung adenocarcinoma by inducing autophagy.…”

Section: Discussionsupporting

confidence: 88%

“…35 Zhang et al demonstrated that tetrandrine inhibited HCC metastasis through modulating the autophagy-dependent Wnt/β-catenin and MTA1 signaling, and autophagic cell death acted as a barrier against metastasis. 36 Consistent with these studies, our findings indicated that XAG suppressed HCC cell metastasis by inducing autophagic cell death.…”

Section: Discussionsupporting

confidence: 88%

“…18,19 Therefore, we also examined the effect of XAG on autophagy and its relation to metastasis inhibition. 18,19 Therefore, we also examined the effect of XAG on autophagy and its relation to metastasis inhibition.…”

Section: Xag Induces Autophagy In Hcc Cellsmentioning

confidence: 99%

“…Numerous studies have shown a crucial role of autophagy in tumor metastasis, several natural compounds exhibit anti-metastatic activity through induction or inhibition of autophagy. 18,19 Therefore, we also examined the effect of XAG on autophagy and its relation to metastasis inhibition. Following a 24-hour XAG treatment, the formation of AVO was detected by acridine orange staining as an indicator of autophagy.…”

Section: Xag Induces Autophagy In Hcc Cellsmentioning

confidence: 99%

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Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Yang

Xie

Liu

et al. 2019

Cell Biochemistry & Function

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Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti-metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3-methyadenine (3-MA) or knockdown of the pro-autophagy Beclin-1 effectively abrogated the XAG-induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p-AMPK while decreasing p-mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy-mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti-metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti-tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti-metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC. KEYWORDSAMPK/mTOR, autophagy, HCC, metastasis, xanthoangelol Xiuwei Yang and Jing Xie are co-first authors and contributed equally to this work.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

Section: Xag Induces Autophagy In Hcc Cellsmentioning

confidence: 99%

Section: Xag Induces Autophagy In Hcc Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Yang

Xie

Liu

et al. 2019

Cell Biochemistry & Function

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“…68 Processes of autophagy include mitophagy (for mitochondria), pexophagy (for peroxisomes), ER-phagy (for endoplasmic reticulum), or ribophagy (for ribosomes), depending on which organelles are targeted for specific autophagic degradation. 15,70,71 Pharmacological inhibitors of autophagy have been used extensively in various cellular conditions to delineate the molecular mechanism of autophagy and the effect of these inhibitors on autophagy. Under certain conditions, cells may undergo autophagic death, if intracellular survival pathways are blocked during autophagy.…”

Section: Cq Inhibits Lysosomal Acidificationmentioning

confidence: 99%

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

2019

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Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

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Autophagy inhibition enhances anti‐pituitary adenoma effect of tetrandrine

Lyu

Yin

et al. 2021

Phytotherapy Research

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Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 μM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 μM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

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The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells

Cited by 58 publications

References 39 publications

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

Autophagy inhibition enhances anti‐pituitary adenoma effect of tetrandrine

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