Oxymatrine targets EGFRp-Tyr845 and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells

Guo, Bingyu; Zhang, Tingting; Su, Jingyuan; Wang, Kaiwen; Li, Xiaoming

doi:10.1007/s00280-014-2651-1

Cited by 53 publications

(43 citation statements)

References 27 publications

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“…Consistent with several previous studies that have reported the antitumor effects of matrine on cancer cells (18)(19)(20), the present study reinforced the findings of the anti-proliferative effects of oxymatrine in bladder cancer cells. The MTT assay indicated that oxymatrine decreased the cell survival rate in a dose-and time-dependent manner, which indicates Apoptotic ratio could not be analyzed for 2.50 mg/ml oxymatrine as necrosis occurred in a high number of cells and was therefore difficult to clearly determine.…”

Section: Discussionsupporting

confidence: 93%

Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest

Zhang²,

Liu

et al. 2017

Oncology Letters

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Abstract.Oxymatrine has been shown to exert an antitumor effect on several types of cancer cells. However, the role of oxymatrine in bladder cancer has not yet been evaluated. The present study was designed to investigate the potential anti-proliferative effect of oxymatrine on bladder cancer T24 cells and the possible mechanisms involved. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine cell growth, and the cell morphology was examined using hematoxylin and eosin staining, wrights' staining and electron microscopy. The caspase-3 and survivin mRNA and protein levels were assessed using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The expression of tumor protein p53 (p53), Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) were analyzed using immunohistochemistry. Oxymatrine inhibited the proliferation of the T24 cells in a dose-and time-dependent manner. Oxymatrine also induced apoptosis and cell cycle arrest in the cells, in association with the upregulation of caspase-3 and Bax, and the downregulation of survivin, Bcl-2 and p53 expression. Overall, oxymatrine inhibits the proliferation of human bladder cancer cells by inducing apoptosis and cell cycle arrest via mechanisms that involve p53-Bax signaling and the downregulation of survivin expression. IntroductionBladder cancer is one of the most common malignant tumors of the urinary system worldwide, affecting 16.6 per 100,000 males and 3.6 per 100,000 females (1). Although surgery is the usual and effective way to treat bladder cancer, the 5-year recurrence rate is ~50% following surgical treatment (2,3). At present, intravesical chemotherapy is the most frequently used method to prevent the recurrence of bladder cancer, subsequent to surgery (4). However, chemotherapy is often associated with multidrug resistance and toxic side effects, with little specificity to cancer cells, which elucidates the challenges of applying chemotherapy to bladder cancers. Natural compounds have previously emerged as a potential treatment for cancer therapy; therefore, natural compounds may be a promising target for bladder cancer therapy.Matrine, the active compound that may be extracted from the Chinese herb Sophora flavecens, has previously been used to treat chronic hepatitis B, allergic dermatitis and hypoleukocytosis, in China (5,6). Matrine may transform into oxymatrine, which may also be extracted from Sophora flavecens, and the nitrogen-oxygen bond may split under certain conditions transforming oxymatrine back to matrine (7). Several studies have demonstrated the multiple beneficial effects of matrine, including anti-arrhythmia (8), anti-inflammation (9,10) and anti-fibrosis (11,12) effects, with minimal side effects reported. In addition, previous studies have shown that matrine induces apoptosis in several cancer cell lines, including breast cancer MCF-7 cells (13) and pancreatic cancer PANC1 cells (14), using various mechanisms, which potentiate the role of...

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Section: Discussionsupporting

confidence: 93%

Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest

Zhang²,

Liu

et al. 2017

Oncology Letters

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“…metastasis and tumor-induced angiogenesis [17][18][19], which makes it an attractive target in cancer therapy. It has been reported that oxymatrine could suppress the proliferation and invasion of gastric cancer cells through EGFR-related signaling pathway [27]. We found that the phosphorylation level of EGFR was dramatically decreased with the increasing concentrations of WM130, suggesting that the effect of WM130 on HCC cells may be through the suppression of EGFR phosphorylation and EGFR-mediated signaling pathway.…”

Section: Wm130 Inhibited the Growth Of Hcc Xenograft Tumors In Nude Micementioning

confidence: 84%

Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways

Qian

Liu

et al. 2015

Cancer Letters

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“…OMT has been extensively investigated for antitumor effects against various cancers [15], including lung [12], gastric [13], pancreatic [11], and breast [14]. However, to the best of our knowledge, the antitumor effects of OMT on GBM have yet to be fully investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Previous in vitro and in vivo studies have shown that OMT inhibits cell proliferation and induces apoptosis in various types of cancers [11–15]. OMT has also been shown to decrease the migratory ability of different cancer cell lines [13, 15]. In this study, we investigate the anticancer properties of OMT on human glioma cells and evaluate their underlying mechanisms.…”

Section: Introductionmentioning

confidence: 98%

Oxymatrine Inhibits Proliferation and Migration While Inducing Apoptosis in Human Glioblastoma Cells

Liu

Wang

et al. 2016

BioMed Research International

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Oxymatrine (OMT), an alkaloid derived from the traditional Chinese medicine herb Sophora flavescens Aiton, has been shown to exhibit anticancer properties on various types of cancer cells. In this study, we investigate the anticancer properties of OMT on human glioblastoma (GBM) cells and evaluate their underlying mechanisms. MTT assays were performed and demonstrated that OMT significantly inhibits the proliferation of GBM cells. Flow cytometry suggested that OMT at a concentration of 10−5 M may induce apoptosis in U251 and A172 cells. Western blot analyses demonstrated a significant increase in the expression of Bax and caspase-3 and a significant decrease in expression of Bcl-2 in both U251 and A172 cells. Additionally, OMT was found by transwell and high-content screening assays to decrease the migratory ability of the evaluated GBM cells. These findings suggest that the antitumor effects of OMT may be the result of inhibition of cell proliferation and migration and the induction of apoptosis by regulating the expression of apoptosis-associated proteins. OMT may represent a novel anticancer therapy for the treatment of GBM.

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Oxymatrine targets EGFRp-Tyr845 and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells

Abstract: Oxymatrine effectively suppressed the phosphorylation of EGFR (Tyr845), and EGFR was the target of oxymatrine.

Cited by 53 publications

References 27 publications

Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest

Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest

Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways

Oxymatrine Inhibits Proliferation and Migration While Inducing Apoptosis in Human Glioblastoma Cells

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