&lt;p&gt;Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway&lt;/p&gt;

Wang, Yanshi; Yang, Shaojie; Zhang, Shanshan; Wu, Xin

doi:10.2147/cmar.s245696

Cited by 11 publications

(7 citation statements)

References 37 publications

(39 reference statements)

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“…Oxymatrine can induce pancreatic cancer cells apoptosis through affecting the ratio of Bax/ Bcl2 and release of mitochondrial cytochrome c, 18 and cause the human bladder cancer cell apoptosis and cell cycle arrest. 19 Oxymatrine inhibits cell proliferation via attenuation of the RAS/ERK pathway, 20 abolishing the PI3K expression, 21,22 suppression of EGFR signaling, 15 and deactivating STAT5. 23 Furthermore, oxymatrine combined with chemotherapeutic agents could enhance their anti-cancer effect.…”

Section: Discussionmentioning

confidence: 99%

<p>Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated Aerobic Glycolysis</p>

Li¹,

Sun²,

Xu³

et al. 2020

CMAR

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Background Colorectal cancer (CRC), a type of highly occurred intestinal cancer at present, is prone to metastasis at the later stage of chemotherapy. Looking for the anti-metastatic agents from natural compounds attracted much concern. Here, it aims to demonstrate whether oxymatrine, an anti-cancer natural compound, has anti-metastatic activity and its potential significance in clinic. Materials and Methods Wound healing assay and transwell assay were for evaluating the effect of oxymatrine on cell migration and invasion in vitro. Anti-metastatic action in vivo was determined by hepatic metastasis of colorectal cancer cells in mice. Results Oxymatrine can significantly inhibit cancer cell migration and invasion in vitro. The production of ATP, pyruvate, and lactate was suppressed in CRC cells under the treatment of oxymatrine, as well as the glucose consumption. Meantime, extracellular acidification rates (ECR) were evidently attenuated although the oxygen consumption rates (OCR) were not affected. Both clued that oxymatrine inhibition of metastasis is possibly related to blocking aerobic glycolysis. Subsequent results indicated that pyruvate kinase M2 (PKM2) not hexokinase (HK) and phosphofructokinase (PFK) were involved in oxymatrine blocking glycolysis as the PKM2 kinase activity and expression were inhibited by oxymatrine and the PKM2 activator, TEPP-46, can reverse in part the effect of oxymatrine induced in CRC cells. Furthermore, this process was also mediated by inhibition of glucose transporter 1 (GLUT1). Finally, the in vivo metastatic model in mice showed both 20 mg/kg and 40 mg/kg oxymatrine significantly inhibit liver metastasis of CRC cells in mice, and PKM2 and GLUT1 expression in liver of the oxymatrine-treated group is declined. Conclusion Oxymatrine exerted anti-metastatic activity dependent on inhibition of PKM2-mediated aerobic glycolysis. It is not only an anti-cancer agent but also a potential anti-metastatic compound with clinical application significance.

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Section: Discussionmentioning

confidence: 99%

<p>Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated Aerobic Glycolysis</p>

Li¹,

Sun²,

Xu³

et al. 2020

CMAR

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“…By detecting cell apoptosis, it was found that oxymatrine can enhance the expression of cleaved asparaginase 3 and Bax, and attenuate the expression of Bcl-2, which further leads to the increase of apoptosis, indicating that oxymatrine can increase the vulvar scale. Antitumor effect of vulva squamous cell carcinoma(VSCC)cells ( 34 ). Similarly, matrine not only reduces the expression level of Bcl-2 and increases the expression of caspase-8, but also inhibits the viability, and migration and induces apoptosis of ovarian cancer cells by up-regulating the p38MAPK and JNK pathways ( 35 ).…”

Section: Apoptosis and Immunogenic Cell Deathmentioning

confidence: 99%

The function of natural compounds in important anticancer mechanisms

Nan

Zhou

et al. 2023

Front. Oncol.

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The existence of malignant tumors has been a threat to human life, health, and safety. Although the rapid development of radiotherapy, drug therapy, surgery, and local therapy has improved the quality of life of tumor patients, there are still some risks. Natural compounds are widely used in cancer because they are easy to obtain, have a good curative effects and have no obvious side effects, and play a vital role in the prevention and treatment of various cancers. Phenolic, flavonoids, terpenoids, alkaloids, and other natural components of traditional Chinese medicine have certain anti-tumor activities, which can promote apoptosis, anti-proliferation, anti-metastasis, inhibit angiogenesis, change the morphology of cancer cells and regulate immune function, etc., and have positive effects on breast cancer, liver cancer, lung cancer, gastric cancer, rectal cancer and so on. To better understand the effects of natural compounds on cancer, this paper screened out four important pathways closely related to cancer, including cell death and immunogenic cell death, immune cells in the tumor microenvironment, inflammation and related pathways and tumor metastasis, and systematically elaborated the effects of natural compounds on cancer.

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“…The ERK/MAPK pathway regulates a variety of cellular activities, including cell growth and signal transduction (38). A large number of studies have shown that the ERK/MAPK pathway in cancer can regulate the expression of c-Myc mRNA and promote the stability of c-Myc, thus promoting the growth of cancer cells (39)(40)(41)(42). In addition, the ERK/MAPK signaling can increase tumor invasion and metastasis by upregulating the expression of MMP2 and MMP9 (43)(44)(45).…”

Section: Expression Of Ppp1r14dmentioning

confidence: 99%

“…Therefore, it can be observed that PPP1R14D knockdown did reduce the expression of BRAF/MEK/ERK signaling pathway proteins. Since several previous studies (39)(40)(41)(42)(43)(44)(45) have shown that the ERK/MAPK signaling pathway acts as upstream proteins to regulate c-MYc, MMP2 and MMP9 proteins, it was hypothesized that the reduced expression of c-Myc, MMP2 and MMP9 proteins was regulated by ERK/MAPK signaling pathway after PPP1R14D knockdown. However, the internal mechanism of the ERK/MAPK signaling pathway in regulating c-Myc, MMP2 and MMP9 proteins after PPP1R14D knockdown was not thoroughly explored, which is a further limitation to the current study.…”

Section: Expression Of Ppp1r14dmentioning

confidence: 99%

PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway

Cao

Wang

et al. 2022

Int J Oncol

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Protein phosphatase 1 (PP1) inhibitors play a role in tumor progression through different mechanisms. Protein phosphatase 1 regulatory subunit 14D (PPP1R14D) is an inhibitor of PP1. However, the role of PPP1R14D in tumors and its mechanism of action are largely unknown. The purpose of the present study was to investigate the expression, function and mechanism of PPP1R14D in lung adenocarcinoma (LUAD). In the present study, GEPIA database analysis and immunohistochemistry demonstrated that PPP1R14D was highly expressed in LUAD tissues and that the expression of PPP1R14D in LUAD was negatively correlated with the age of patients and positively correlated with the 8th American Joint Committee on Cancer staging among patients. In addition, Kaplan-Meier Plotter database analysis showed that PPP1R14D expression was associated with lower survival rates in patients with LUAD. PPP1R14D knockdown significantly inhibited LUAD cell proliferation, migration and invasion and induced LUAD cell arrest at the G1 phase of the cell cycle. Mechanistic analyses revealed that PPP1R14D knockdown may inhibit cell proliferation, migration and invasion by inactivating PKCα/BRAF/MEK/ERK pathway signaling and its downstream key proteins c-Myc/Cyclin E1-CDK2 and MMP2/MMP9/Vimentin. Moreover, knockdown of PPP1R14D suppressed tumor growth in vivo. All these results showed that PPP1R14D plays an important role in LUAD tumorigenesis and may serve as a potential prognostic factor and therapeutic target in LUAD.

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<p>Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway</p>

Cited by 11 publications

References 37 publications

<p>Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated Aerobic Glycolysis</p>

<p>Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated Aerobic Glycolysis</p>

The function of natural compounds in important anticancer mechanisms

PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway

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