Tetrandrine suppresses human glioma growth by inhibiting cell survival, proliferation and tumour angiogenesis through attenuating STAT3 phosphorylation

Ma, Jiwei; Zhang, Yong; Li, Ru; Ye, Jiecheng; Li, Haiying; Zhang, Yikai; Ma, Zheng-lai; Li, Jinying; Zhong, Xueyun; Yang, Xuesong

doi:10.1016/j.ejphar.2015.06.017

Cited by 33 publications

(17 citation statements)

References 30 publications

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“…Tet inhibits the proliferation, survival and angiogenesis of glioma, breast cancer, colon cancer and non-small cell lung cancer (NSCL) (Gao et al ., 2013; Ma et al ., 2015; Lin et al ., 2016). Tet has also been reported to cause radiosensitivity in esophagal carcinoma and breast cancer and to abrogate radiation-induced G2/M phage arrest to increase apoptosis in nasopharyngeal carcinoma cells (Sun et al ., 2007a, 2007b; Yu et al ., 2011).…”

Section: Discussionmentioning

confidence: 99%

“…The absorbance (OD) of the formazan solution, which reflects the cell growth conditions, was measured at 570 nm using a microplate spectrophotometer (ELx800 BioTek Instruments, LA, USA). The results are represented as the OD ratio of the 20% inhibitory concentration (IC 20 ) of Tet at 24 h, which was calculated and chosen for the following experiments (Ma et al ., 2015). …”

Section: Methodsmentioning

confidence: 99%

“…Tet causes G0/G1 phase arrest, thereby altering radiation-induced G2/M phase arrest in nasopharyngeal carcinoma (Yu et al ., 2011). Tet has also been shown to inhibit glioma cell proliferation by blocking the cell cycle at G0/G1 phase (Ma et al ., 2015), the specific molecular mechanism that regulates radiosensitization requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Zhang

et al. 2016

Biomol Ther (Seoul)

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Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Zhang

et al. 2016

Biomol Ther (Seoul)

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“…[7][8][9][10][11] Of note, tetrandrine has shown to suppress multiple biological activity of human cancer cells via regulating cell viability, migration, invasion, angiogenesis and multidrug resistance of the tumours. [12] Tetrandrine can inhibit proliferation of cancer cells by modulating multiple pathways such as Bcl-2/Bax, [13] STAT3 in glioma cells [14] and IGFBP-5 in human colon cancer cells, [15] PI3K/Akt in prostate cancer cells [16] and caspase in hepatic cellular carcinoma cell. [17] Tetrandrine was also found to induce cytotoxicity and apoptosis of human nasopharyngeal carcinoma cells via inducing ROSdependent mitochondrial and ER stress pathways [18,19] and activating Akt/FOXO3.…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of tetrandrine by inducing pro-death apoptosis and autophagy in human gastric cancer cells

Bai

Liu

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Tetrandrine (Tet), a natural product isolated from Stephania tetrandra, has been reported to be an anti-tumor and anti-inflammatory drug (1)(2)(3)(4)(5)(6)(7)(8). Previously, the present authors have demonstrated that Tet induces cell death in 11 cancer cell lines (1).…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine triggers an alternative autophagy in DU145 cells

2017

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Abstract. Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells. By contrast, it was observed by transmission electron microscopy that Tet induced an accumulation of autophagosomes in the cytoplasm. These contrasting results indicated that Tet triggered an LC3-independent autophagy in DU145 cells. Alkalizing lysosome with chloroquine enhanced Tet-induced cell death. The results of the present study indicated that detection of autophagy in tumor cells may assist in selecting lysosome inhibitors for chemotherapy treatment in prostate cancer. Introduction Tetrandrine (Tet), a natural product isolated fromStephania tetrandra, has been reported to be an anti-tumor and anti-inflammatory drug (1-8). Previously, the present authors have demonstrated that Tet induces cell death in 11 cancer cell lines (1). Tet directly neutralizes the lysosomal acidity, blocks the autophagic flux in the degradation step and causes energetic impairment, which eventually results in cell death (1). By contrast, Tet also acts as an autophagy agonist by inducing the synthesis of reactive oxygen species (3,4,9-11), indicating that Tet may function as a multi-target drug to regulate autophagy in cancer cells. Regardless of the Tet target, the present authors and other groups have previously consistently observed that Tet increases the number of autophagosomes, levels of microtubule-associated protein 1 light chain 3, type II (LC3-II) and the number of enhanced green fluorescent protein-LC3 puncta in cancer cells (1,3,9). DU145, a commonly used prostate cancer cell line for research, is different from PC-3 and LNCaP cells in terms of autophagy regulation (12). As alternative transcripts of autophagy related 5 (ATG5) lack one or two exons in DU145 cells, and this causes the autophagy pathway to be genetically impaired (12). By contrast, DU145 cells exhibited the highest sensitivity to Tet in all of the 11 cancer cell lines that were previously tested by the authors of the present study (1), implying that impairment in autophagy may increase Tet-induced cell death. In order to investigate the role of autophagy on Tet-induced cell death in DU145 cells, the ultrastructural changes following Tet treatment were observed by transmission electron microscopy (TEM). Notably, Tet treatment triggered an accumulation of autophagosomes in this cell line, indicating that alternative autophagy was involved. Materials and methodsTetrandrine and other reagents. Tet (Santa Cr uz Biotechnology, Inc., Dallas, TX, USA) was dissolved as previously described (1)....

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Tetrandrine suppresses human glioma growth by inhibiting cell survival, proliferation and tumour angiogenesis through attenuating STAT3 phosphorylation

Cited by 33 publications

References 30 publications

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Anticancer activity of tetrandrine by inducing pro-death apoptosis and autophagy in human gastric cancer cells

Tetrandrine triggers an alternative autophagy in DU145 cells

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