Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP‐2 and the c‐Raf/MEK/ERK pathway

Fang, Chih Yuan; Wu, Chung Ze; Chen, Pei Ni; Chang, Yi-Chun; Chuang, Chun Yi; Lai, Chih Ting; Yang, Shun Fa; Tsai, Lo Lin

doi:10.1002/tox.22542

Cited by 27 publications

(19 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that blocking the MAPK/ERK signaling cascade can inhibit MMP2 expression and inhibit the metastasis of oral squamous cell carcinoma. 36 Our results showed that oxymatrine not only reduced expression levels of RAS, p-RAF, p-MEK, and p-ERK, but also those of C-MYC and MMP2, similar to the effects of salirasib. Inhibition of upstream protein expression can reduce expression of downstream proteins in the same signaling pathway.…”

Section: Discussionsupporting

confidence: 70%

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

Wang¹,

Yang²,

Zhang³

et al. 2020

CMAR

View full text Add to dashboard Cite

Purpose: To evaluate the anti-tumor effects of oxymatrine in vulvar squamous cell carcinoma (VSCC) cells and to explore the underlying mechanisms. Methods: We selected SW962 and A431 VSCC cell lines. Cell proliferation was examined using MTT assay. Cell cycle and apoptosis were detected using flow cytometry. Migration and invasion were evaluated using transwell and wound-healing assays. The relevant protein expression and signaling pathways were analyzed using Western blotting. Results: Oxymatrine inhibited the proliferation of SW962 and A431 VSCC cells in a timeand dose-dependent manner. Oxymatrine induced cell cycle arrest in the G2/M phase by increasing the protein expression of P21 and decreasing levels of cyclin B1 and CDC2. Oxymatrine upregulated the expression of cleaved-caspase 3 and BAX and downregulated the expression of BCL2, which led to an increase in apoptosis. Oxymatrine also suppressed the migration and invasion of SW962 and A431 cells by reducing levels of MMP2 and MMP9. After treatment with oxymatrine or a RAS inhibitor (salirasib), expression levels of RAS, p-RAF, p-MEK, p-ERK, C-MYC, and MMP2 were reduced. When TGF-β1 was used to stimulate SW962 and A431 cells, the expression of the above proteins increased; this increase was reversed by using oxymatrine or salirasib again. Conclusion: Oxymatrine inhibits proliferation and migration of VSCC cells by blocking the RAS/RAF/MEK/ERK pathway.

show abstract

Section: Discussionsupporting

confidence: 70%

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

Wang¹,

Yang²,

Zhang³

et al. 2020

CMAR

View full text Add to dashboard Cite

show abstract

“…Despite efforts to improve its early diagnosis and treatment, advanced OSCC still has an extremely poor 5-year survival rate of less than 63%, mainly due to high recurrence rates brought about by its ability to invade local tissues and to metastasize [4]. Surgery remains the first-line treatment for a significant proportion of patients with OSCC [5].…”

Section: Introductionmentioning

confidence: 99%

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

Nan

Zhong

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. Methods: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. Results: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. Conclusion: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

show abstract

“…In cardiac fibrosis, danshensu has been found to inhibit β-adrenergic receptor-mediated fibroblast proliferation and collagen-I synthesis primarily by suppressing p38 signaling pathway (28). Recently, one study has shown than salvianolic acid A can prevent OSCC metastasis by inhibiting Raf/MEK/ERK signaling pathway, which subsequently causes reduction of MMP-2 expression (29). To investigate the molecular mechanism involved in sodium danshensu-mediated anti-metastatic effects, we thought of examining the level and activity of conventional MAPKs, including ERK1/2, JNK1/2, and p38.…”

Section: Discussionmentioning

confidence: 99%

Sodium Danshensu Inhibits Oral Cancer Cell Migration and Invasion by Modulating p38 Signaling Pathway

et al. 2020

View full text Add to dashboard Cite

Background: Oral squamous cell carcinoma (OSCC) that comprises about 90% of all oral cancer cases is associated with poor prognosis due to its highly metastatic nature. The majority of OSCC treatment options are related detrimental side-effects. Hypothesis/Purpose: The present study aimed at deciphering the effects of a bioactive phytochemical, sodium danshensu, on human oral cancer cell metastasis. Methods and Results: The treatment of FaDu and Ca9-22 cells with different doses of sodium danshensu (25, 50, and 100 µM) caused a significant reduction in cellular motility, migration, and invasion, as compared to the untreated cells. This effect was associated with a reduced expression of MMP-2, vimentin and N-cadherin, together with an enhanced expression of E-cadherin and ZO-1. Further investigation on the molecular mechanism revealed that treatment with sodium danshensu caused significant reduction in p38 phosphorylation; however, phosphorylation of ERK1/2 significantly decreased only in FaDu cells, whereas p-JNK1/2 did not show any alteration. A combination of p38 and JNK1/2 inhibitors with sodium danshensu also reduced the migration in the FaDu and Ca9-22 cell lines. Conclusion: Collectively, the present study findings reveal that sodium danshensu execute anti-metastatic effect by suppressing p38 phosphorylation in human oral cancer. The study identifies sodium danshensu as a potential natural anticancer agent that can be used therapeutically to manage highly metastatic OSCC.

show abstract

Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP‐2 and the c‐Raf/MEK/ERK pathway

Cited by 27 publications

References 40 publications

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

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

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

Sodium Danshensu Inhibits Oral Cancer Cell Migration and Invasion by Modulating p38 Signaling Pathway

Contact Info

Product

Resources

About