Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

Liu, Ying; Zhang, Yan; Zou, Jilong; Yan, Lei; Yu, Xuezhong; Lü, Peng; Wu, Xianglei; Li, Qiaozhi; Gu, Rui; Zhu, Daling

doi:10.1159/000485536

Cited by 25 publications

(18 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A study has shown halofuginone‐induced autophagy suppresses breast cancer cell migration and invasion . Meanwhile, in osteosarcoma cells, the activation of autophagy is associated with the suppression of EMT . In the study, we used 3‐MA to inhibit autophagy and observed the effects of TQ on migration, invasion and EMT in RCC cell lines 786‐O and ACHN.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

et al. 2018

View full text Add to dashboard Cite

Thymoquinone (TQ, 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti‐tumor efficiency in various cancers. Autophagy is a self‐digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786‐O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ‐treated RCC cells, and then found that autophagy was induced by TQ in 786‐O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy‐dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ‐induced autophagy in RCC treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Several therapy, such as osteroprotegerin, RANK-Fc, PTHrp antibodies, and Vitamin-D analogues, are under phase I to III studies. Other target therapy, such as anti-MMP-9,anti-IGF-1R, Quercetin, Osthole and activating aromatic hydrocarbon receptor, were reported in rescent [120, 122-126]. Current treatments mainly target the RANK-RANKL pathway and PTHrP signaling.…”

Section: Therapeutic and Molecular Interventionsmentioning

confidence: 99%

Molecular Regulation of Bone Metastasis Pathogenesis

Yiang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.

show abstract

“…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%

“…Given the established role of AMPK/mTOR axis in autophagy, 21,22 we analyzed the status of AMPK/mTOR pathway mediators in XAGinduced autophagy in HCC. Cells treated with XAG exhibited an increase in the levels of phosphorylated AMPK and reduced the levels of phosphorylated mTOR, without affecting the expression of total AMPK and mTOR ( Figure 4A).…”

Section: Xag Induces Hcc Autophagy By Activating Ampk/mtor Signalinmentioning

confidence: 99%

See 1 more Smart Citation

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

Yang

Xie

Liu

et al. 2019

Cell Biochemistry & Function

View full text Add to dashboard Cite

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.

show abstract

Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

Cited by 25 publications

References 54 publications

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

Molecular Regulation of Bone Metastasis Pathogenesis

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

Contact Info

Product

Resources

About