scholarly journals Ethanol Extracts of Fruiting Bodies ofAntrodia cinnamomeaSuppress CL1-5 Human Lung Adenocarcinoma Cells Migration by Inhibiting Matrix Metalloproteinase-2/9 through ERK, JNK, p38, and PI3K/Akt Signaling Pathways

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ying-Yi Chen ◽  
Fon-Chang Liu ◽  
Pei-Yu Chou ◽  
Yi-Chung Chien ◽  
Wun-Shaing Wayne Chang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Lung Adenocarcinoma ◽  
Cancer Metastasis ◽  
Human Lung ◽  
Gelatin Zymography ◽  
Matrix Metalloproteinase 2 ◽  
Dependent Manner ◽  
Fruiting Bodies ◽  
Anticancer Activities ◽  
Human Lung Adenocarcinoma

Cancer metastasis is a primary cause of cancer death.Antrodia cinnamomea(A. cinnamomea), a medicinal mushroom in Taiwan, has shown antioxidant and anticancer activities. In this study, we first observed that ethanol extract of fruiting bodies ofA. cinnamomea(EEAC) exerted a concentration-dependent inhibitory effect on migration and motility of the highly metastatic CL1-5 cells in the absence of cytotoxicity. The results of a gelatin zymography assay showed thatA. cinnamomeasuppressed the activities of matrix metalloproteinase-(MMP-) 2 and MMP-9 in a concentration-dependent manner. Western blot results demonstrated that treatment withA. cinnamomeadecreased the expression of MMP-9 and MMP-2; while the expression of the endogenous inhibitors of these proteins, that is, tissue inhibitors of MMP (TIMP-1 and TIMP-2) increased. Further investigation revealed thatA. cinnamomeasuppressed the phosphorylation of ERK1/2, p38, and JNK1/2.A. cinnamomeaalso suppressed the expressions of PI3K and phosphorylation of Akt. Furthermore, treatment of CL1-5 cells with inhibitors specific for PI3K (LY 294002), ERK1/2 (PD98059), JNK (SP600125), and p38 MAPK (SB203580) decreased the expression of MMP-2 and MMP-9. This is the first paper confirming the antimigration activity of this potentially beneficial mushroom against human lung adenocarcinoma CL1-5 cancer cells.

scholarly journals Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Ping Huang ◽  
Chien-Hang Ni ◽  
Chi-Cheng Lu ◽  
Jo-Hua Chiang ◽  
Jai-Sing Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Gelatin Zymography ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Human Bladder Cancer ◽  
Human Bladder

Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP)-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative ofblister beetleswhich is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA), and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potentialviasuppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells

2017 ◽  
Vol 45 (02) ◽  
pp. 369-384 ◽  
Author(s):  
San Fu ◽  
Yanfang Yang ◽  
Dan Liu ◽  
Yan Luo ◽  
Xiaochuan Ye ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Human Lung ◽  
A549 Cells ◽  
Mitochondrial Pathway ◽  
Total Flavonoids ◽  
Dependent Manner ◽  
Protein Levels ◽  
Human Lung Adenocarcinoma ◽  
Dose Dependent

In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.

scholarly journals Sinomenine Inhibits Migration and Invasion of Human Lung Cancer Cell through Downregulating Expression of miR-21 and MMPs

2020 ◽  
Vol 21 (9) ◽  
pp. 3080 ◽  
Author(s):  
Kun-Hung Shen ◽  
Jui-Hsiang Hung ◽  
Yi-Ching Liao ◽  
Shu-Ting Tsai ◽  
Ming-Jiuan Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
E Cadherin

Sinomenine is an alkaloid derived from Sinomenium acutum. Recent studies have found that sinomenine can inhibit various cancers by inhibiting the proliferation, migration and invasion of tumors and inducing apoptosis. This study aims to investigate the effect and mechanism of sinomenine on inhibiting the migration and invasion of human lung adenocarcinoma cells in vitro. The results demonstrate that viabilities of A549 and H1299 cells were inhibited by sinomenine in a dose-dependent manner. When treated with sub-toxic doses of sinomenine, cell migration and invasion are markedly suppressed. Sinomenine decreases the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9, and the extracellular inducer of matrix metalloproteinase (EMMPRIN/CD147), but elevates the expression of reversion-inducing cysteine-rich proteins with kazal motifs (RECK) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. In addition, sinomenine significantly increases the expression of the epithelial marker E-cadherin but concomitantly decreases the expression of the mesenchymal marker vimentin, suggesting that it suppresses epithelial–mesenchymal transition (EMT). Moreover, sinomenine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. The downregulation of miR-21 decreases cell invasion, while the upregulation of miR-21 increases cell invasion. Furthermore, the downregulation of miR-21 stimulates the expression of RECK, TIMP-1/-2, and E-cadherin, but reduces the expression of MMP-2/-9, EMMPRIN/CD147, and vimentin. Taken together, the results reveal that the inhibition of A549 cell invasion by sinomenine may, at least in part, be through the downregulating expression of MMPs and miR-21. These findings demonstrate an attractive therapeutic potential for sinomenine in lung cancer anti-metastatic therapy.

scholarly journals Tetracycline and Glutathione Inhibit Matrix Metalloproteinase Activity: An In Vitro Study Using Culture Supernatants of L929 and Dalton Lymphoma Cell Lines

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Gajanan Kendre ◽  
Rahul Raghavan ◽  
Sanith Cheriyamundath ◽  
Joseph Madassery
Keyword(s):  
Matrix Metalloproteinase ◽  
Inhibitory Activity ◽  
Cancer Metastasis ◽  
Reduced Glutathione ◽  
Gelatin Zymography ◽  
Matrix Metalloproteinase 2 ◽  
Clinical Effects ◽  
Dalton Lymphoma ◽  
Metalloproteinase Activity

Tetracycline and glutathione inhibited the protease activities of matrix metalloproteinase-2 and matrix metalloproteinase-9 expressed by mouse fibrosarcoma cells (L929) and Dalton lymphoma cells, respectively. The inhibitory activity of the tetracycline may be due to its ability to chelate metal ions such as calcium and zinc. Gelatin-zymography technique was used to demonstrate the inhibitory activity of both tetracycline and glutathione. The intensity of the bands corresponding to metalloproteinase activity in zymography gel was reduced in the presence of 50–100 μg/mL of tetracycline. The presence of 10–100 μg/mL of tetracycline in the medium increased the adherence of L929 cancer cells. These results clearly indicate the antimetastatic property of tetracycline. Reduced glutathione, a compound which is produced endogenously by the cells to maintain the redox status, was shown to inhibit the matrix metalloproteinase activity (in vitro). Therefore, it is assumed that decreased glutathione levels in synovial fluids or plasma might increase the activity of MMP. Reduced glutathione at 100 μg/mL inhibited the metalloproteinase activity in gelatin-zymographic gel. As both tetracycline and glutathione exhibited an inhibitory effect on matrix metalloproteinase activity, it was of great interest to check their clinical effects on various MMP associated pathological conditions such as cancer metastasis and arthritis. Here we report that tetracycline and reduced glutathione inhibited the activity of MMP2 completely and activity of MMP9 partly.

scholarly journals Andrographolide Induces Noxa-Dependent Apoptosis by Transactivating ATF4 in Human Lung Adenocarcinoma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Junqian Zhang ◽  
Chunjie Li ◽  
Li Zhang ◽  
Yongqing Heng ◽  
Tong Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Human Lung ◽  
High Dose ◽  
Dependent Manner ◽  
Human Lung Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Induced Apoptosis

Lung adenocarcinoma is the most common pathological type of lung cancer with poor patient outcomes; therefore, developing novel therapeutic agents is critically needed. Andrographolide (AD), a major active component derived from the traditional Chinese medicine (TCM) Andrographis paniculate, is a potential antitumor drug, but the role of AD in lung adenocarcinoma remains poorly understood. In the present study, we demonstrated that AD inhibited the proliferation of broad-spectrum lung cancer cell lines in a dose-dependent manner. Meanwhile, we found that a high dose of AD induced Noxa-dependent apoptosis in human lung adenocarcinoma cells (A549 and H1299). Further studies revealed that Noxa was transcriptionally activated by activating transcription factor 4 (ATF4) in AD-induced apoptosis. Knockdown of ATF4 by small interfering RNA (siRNA) significantly diminished the transactivation of Noxa as well as the apoptotic population induced by AD. These results of the present study indicated that AD induced apoptosis of human lung adenocarcinoma cells by activating the ATF4/Noxa axis and supporting the development of AD as a promising candidate for the new era of chemotherapy.

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