Ligustrazine inhibits B16F10 melanoma metastasis and suppresses angiogenesis induced by Vascular Endothelial Growth Factor

Chen, Lei; Lu, Yin; Wu, Jiaming; Xu, Bo; Zhang, Lijuan; Gao, Ming; Zheng, Shizhong; Wang, Aiyun; Zhang, Changbin; Zhang, Wei Wei; Lei, Na

doi:10.1016/j.bbrc.2009.06.042

Cited by 45 publications

(37 citation statements)

References 21 publications

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“…Previous studies have focused on identifying the underlying molecular mechanisms of TMP activity due to its well established antitumor effect and its ability to reverse resistance to chemotherapy treatments, while causing less adverse reactions (16,17). For example, TMP was able to inhibit the growth and migration of glioma by regulating calcium influxes (21) and additionally, TMP was revealed to decrease the metastases of melanoma by suppressing vascular endothelial growth factor activity (22). Furthermore, TMP has been identified to serve a function in the reversal of multidrug resistance in a number of types of malignant tumor, including reversing the multi-drug resistance in hepatocellular carcinoma via inhibiting P-gp, MRP2, MRP3 and MRP5 (16); TMP could effectively reverse multi-drug resistance of bladder cancer cells and its mechanisms may be associated with the alteration of MRP1, GST, BCL-2 and TOPO-II (23); TMP as a salvage agent for patients with relapsed or refractory non-Hodgkin's lymphoma may also be associated with its effect on the expression of P-gp (24).…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Shen¹,

Zeng²,

Pan³

et al. 2018

Oncol Lett

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Abstract. Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in a number of types of malignant epithelial cancer. However, the mode of action of TMP on breast cancer cells remains unknown. The aim of the present study was to investigate the regulatory effect of TMP on breast cancer cells and its underlying molecular mechanism of action. Different concentrations of TMP were used to treat breast cancer cells, and subsequently, the effects on the viability, apoptosis, and migration and invasion abilities were determined. In addition, the expression and activity levels of the protein kinase B (Akt) signaling pathway and caspase-3 were explored via reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study revealed that TMP significantly inhibited the viability, migration and invasion rates, and increased the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The minimum effective dose was ~1,600 µM. Additional mechanistic studies demonstrated that 1,600 and 3,200 µM TMP significantly decreased the gene expression and activity of Akt and increased the activity of caspase-3. This mechanism may be responsible for the inhibition of viability, migration and invasion, and activation of apoptosis in breast cancer cells. The results of the present study suggested that TMP may be used in chemotherapy against breast cancer.

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Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Shen¹,

Zeng²,

Pan³

et al. 2018

Oncol Lett

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“…the mechanism of how chemotherapy effectively reduces IL-8 expression in ovarian cancer remains poorly understood. tMp has been previously described in the literature as an antioxidant and anti-inflammatory agent, capable of inhibiting cell migration and proliferation in glioma cells (13) and melanoma metastasis (14). Our previous data demonstrated that tMp suppresses IL-8 production in lipopolysaccharidestimulated human umbilical vein endothelial cells (25).…”

Section: Discussionmentioning

confidence: 82%

“…previous data have demonstrated that tMp suppresses glioma cell line activity, including growth and migration, by inhibiting calcium influx (13). Similarly, Chen et al reported that tMp inhibits melanoma metastasis in vivo partly through suppressing VeGF activity (14). therefore, tMp may be a potentially effective option for treatment of both inflammation and tumors.…”

Section: Tetramethylpyrazine Inhibits Migration Of Skov3mentioning

confidence: 92%

Tetramethylpyrazine inhibits migration of SKOV3 human ovarian carcinoma cells and decreases the expression of interleukin-8 via the ERK1/2, p38 and AP-1 signaling pathways

Yang¹

2011

Oncol Rep

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Abstract. expression by melanoma cells may influence their metastatic capabilities. tetramethylpyrazine (tMp) from Ligusticum wallichil Franch. possesses anti-inflammatory and antitumor activities. It has recently been suggested that autocrine IL-8 may play a role in tumor cell survival, invasion and migration. the role of tMp in association with IL-8 in the tumor cell migratory process remains unclear. the purpose of the present study was to determine whether TMP influences the migratory ability of a human ovarian carcinoma cell line (sKOV3) via regulation of IL-8 expression in vitro. Cell counts showed that treatment of sKOV3 with tMp (25-100 µg/ml) for 24 h did not decrease cell numbers, while an effect of tMp on the down-regulation of the expression of IL-8 was observed. In addition, migration of sKOV3 cells was suppressed after treatment with tMp (25-100 µg/ml) for 24 h. therefore, expression of IL-8 by sKOV3 cells correlates with their metastatic potential. Western blot analysis revealed that erK1/2 and p38 phosphorylation was blocked by tMp. Furthermore, IL-8 mrNA expression was inhibited significantly after co-incubation with PD98059 (erK inhibitor) and sB203580 (p38 inhibitor), respectively. Notably, these changes were the results of activator protein-1 (Ap-1) activity suppression rather than that of NF-κB. Our data suggest that tMp may inhibit tumor cell invasion and migration, at least in part, through its down-regulation of IL-8 expression. Our results provide evidence that anti-inflammation plays an important role in integrative cancer therapies. IntroductionThe functional relationship between inflammation and cancer is widely accepted. Inflammation is a critical component of tumor progression, such as tumor cell metastasis (1). Metastasis, a complex and multiple process in which tumor cells spread from the primary site to distant organs, is one of the most common causes of morbidity and mortality in patients with ovarian carcinoma. the migratory capacity of cancer cells can be regulated by various factors including growth factors and cytokines (2), such as CXC-chemokine IL-8 (CXCL-8), a pro-inflammatory cytokine initially described as a neutrophil and monocyte chemoattactant, which modulates monocyte adhesion to endothelium and vascular smooth muscle cell migration (3-5). A direct correlation has also been demonstrated between overexpressed IL-8 and the increased metastasis of tumor cells (6-8). Evidence has confirmed that tumor cells are able to respond to the autocrine release of IL-8, which enables tumor cells to have an additional growth and progression advantage (9). De Larco et al (10) reported that the concentration gradient of IL-8 produced by tumor cells, which is higher at the primary tumor site than that at noncancerous sites, promotes distant metastasis of tumor cells. Moreover, IL-8 can recruit neutrophils to the primary tumor site through its chemoattractant capacity. In response to IL-8, the recruited neutrophils release proteases and heparanase which hydrolyze components of the ext...

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“…In vitro cell migration assays were performed using 24-well transwell plates (Corning Incorporated Costar, Lindfield, NSW, Australia) [15] . B16F10 cells were grown to a confluence of 80% and incubated with different concentrations of luteolin and 1% O 2 for 24 h. After trypsinization, and resuspension in serum-free DMEM, the cell concentration was adjusted to 1×10 6 before seeding into 24-well transwell plates.…”

Section: Cell Migration Assaymentioning

confidence: 99%

Luteolin reduces the invasive potential of malignant melanoma cells by targeting β3 integrin and the epithelial-mesenchymal transition

et al. 2012

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Aim: To investigate whether luteolin, a highly prevalent flavonoid, reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal. Methods: Murine malignant melanoma B16F10 cells were exposed to 1% O 2 for 24 h. Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay, respectively. EMT-related proteins, such as E-cadherin and N-cadherin, were examined using Western blotting. Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1×10 6 cells in 0.2 mL per mouse) via the lateral tail vein. The mice were treated with luteolin (10 or 20 mg/kg, ip) daily for 23 d. On the 23rd day after tumor injection, the mice were sacrificed, and the lungs were collected, and metastatic foci in the lung surfaces were photographed. Tissue sections were analyzed with immunohistochemistry and HE staining. Results: Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips, which was accompanied by increased cellular adhesion and invasion. Luteolin (5−50 µmol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner. Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation), which was reversed by luteolin (5 μmol/L). In B16F10 cells, luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway. In experimental metastasis model mice, treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%. Furthermore, the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues. Conclusion: Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin, suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent.

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Ligustrazine inhibits B16F10 melanoma metastasis and suppresses angiogenesis induced by Vascular Endothelial Growth Factor

Cited by 45 publications

References 21 publications

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Tetramethylpyrazine inhibits migration of SKOV3 human ovarian carcinoma cells and decreases the expression of interleukin-8 via the ERK1/2, p38 and AP-1 signaling pathways

Luteolin reduces the invasive potential of malignant melanoma cells by targeting β3 integrin and the epithelial-mesenchymal transition

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