Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

Xiao, Wei

doi:10.3892/ijo.2012.1375

Cited by 20 publications

(17 citation statements)

References 30 publications

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“…It has already been reported that TMP could be used as an antagonist to scavenge ROS for treatment of cardiovascular and cerebrovascular diseases [35]. Recent finding shows that TMP acts as an inhibitor of cyclooxygenase-2 and may have an antitumour effect on non-small cell lung cancer [46]. Moreover, TMP can induce mitochondrial mediated apoptosis in hepatic stellate cells and is considered as a potential choice for the treatment of hepatic fibrosis [34].…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM

Lan

Guo

et al. 2017

Bioscience Reports

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The natural small molecule compound: 2,3,5,6-tetramethylpyrazine (TMP), is a major component of the Chinese medicine Chuanxiong, which has wide clinical applications in dilating blood vessels, inhibiting platelet aggregation and treating thrombosis. Recent work suggests that TMP is also an antitumour agent. Despite its chemotherapeutic potential, the mechanism(s) underlying TMP action are unknown. Herein, we demonstrate that TMP binds to mitochondrial transcription factor A (TFAM) and blocks its degradation by the mitochondrial Lon protease. TFAM is a key regulator of mtDNA replication, transcription and transmission. Our previous work showed that when TFAM is not bound to DNA, it is rapidly degraded by the ATP-dependent Lon protease, which is essential for mitochondrial proteostasis. In cultured cells, TMP specifically blocks Lon-mediated degradation of TFAM, leading to TFAM accumulation and subsequent up-regulation of mtDNA content in cells with substantially low levels of mtDNA. In vitro protease assays show that TMP does not directly inhibit mitochondrial Lon, rather interacts with TFAM and blocks degradation. Pull-down assays show that biotinylated TMP interacts with TFAM. These findings suggest a novel mechanism whereby TMP stabilizes TFAM and confers resistance to Lon-mediated degradation, thereby promoting mtDNA up-regulation in cells with low mtDNA content.

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Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM

Lan

Guo

et al. 2017

Bioscience Reports

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“…Tetramethylpyrazine (TMPZ), a major bioactive component of the traditional Chinese medicine Chuanxiong, has been widely used in the clinical treatment of neurovascular and cardiovascular diseases (1,2). Although a number of studies have demonstrated that TMPZ inhibits proliferation and induces apoptosis in rat C6 glioma and human adenocarcinoma cells (3,4), to the best of our knowledge, there are no studies reporting its effects in gastric cancer. The exact mechanism of action of TMPZ is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells

Liu

et al. 2013

Oncology Letters

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Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese medicinal herb Chuanxiong and several studies have shown it to possess anticancer properties. However, its effectiveness in gastric cancer and its cellular mechanisms are relatively unknown. The present study aimed to investigate the effect of TMPZ on SGC7901 cells, and it was demonstrated that a high dose of TMPZ inhibited cell viability and induced apoptosis by stimulating AMP-activated protein kinase (AMPK) through the generation of reactive oxygen species (ROS). Furthermore, TMPZ-induced apoptosis resulted in the sequential events beginning with the translocation of Bax, the collapse of mitochondrial membrane potential (ΔΨm), the release of cytochrome c and the activation of caspase-9 and -3. Each of these events was inhibited by compound C, a pharmacological inhibitor of AMPK. To the best of our knowledge, these results demonstrate for the first time that the induction of apoptosis by TMPZ in gastric cancer cells is associated with the activation of the ROS/AMPK pathway. AMPK activation induces apoptosis through the mitochondrial apoptotic pathway. In addition, these results raise the possibility that TMPZ may have a future therapeutic role in gastric cancer.

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“…TMPZ has also anti-inflammatory actions in a rat asthma model [9]. Most interestingly, TMPZ has been reported to have anti-carcinogenic effects in various cancers, including breast cancer [10], ovarian cancer [11], lung cancer [12][13][14][15], hepatocellular cancer [16], glioma [17,18], leukemia [19] and melanoma [20]. In lung cancer, TMPZ has been found to affect invasion and metastasis [13,14].…”

mentioning

confidence: 99%

“…In lung cancer, TMPZ has been found to affect invasion and metastasis [13,14]. Most recently, Zheng et al revealed cyclooxygenase (COX)-2, a crucial enzyme in carcinogenesis, to be a molecular target of TMPZ [12]. In vitro treatment of A549 cells with TMPZ resulted in a significant inhibition of invasion, associated with reduced activities of COX-2 and MMP-2/TIMP-2 [12].…”

mentioning

confidence: 99%

Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria- dependent apoptosis in lung cancer cells

Huang¹,

Liu²,

Ruan³

et al. 2018

neo

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Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese herb Chuanxiong. Several studies have shown its anti-cancer properties. However, its functions in lung cancer and the underlying cellular mechanisms are relatively unknown. Our present study aimed to investigate the effects of TMPZ on A549 and 95D cells. The MTT assay showed that TMPZ decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that TMPZ strongly suppressed colony formation ability in A549 and 95D cells. Flow cytometric analysis revealed that TMPZ induced S phase arrest in lung cancer cells. In addition, TMPZ induced apoptosis, as shown by the results of propidium iodide/Annexin V double-staining. Furthermore, TMPZ decreased mitochondrial membrane potential (∆Ψm) in a dose-dependent manner. Finally, western blot analysis of TMPZ-treated cells revealed the activation of Caspase-3 and the increase of the ratio of Bax/Bcl-2. These results demonstrated that TMPZ could suppress carcinogenesis of lung cancer cells through blocking cell cycle and inducing mitochondria-dependent apoptosis by regulating Caspase-3 and Bax/Bcl-2, suggesting that TMPZ may be a promising drug to treat lung cancer.

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Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

Cited by 20 publications

References 30 publications

Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM

Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM

Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells

Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria- dependent apoptosis in lung cancer cells

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