Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway

  • Authors:
    • De Jiao
    • Xue Dong Zhang
  • View Affiliations

  • Published online on: April 28, 2016     https://doi.org/10.3892/or.2016.4777
  • Pages: 342-348
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

As a main active compound in the bark of waxberry (Myrica rubra), myricetin is a macrocyclic diarylheptanoid, and can trigger the apoptosis of HeLa and PC3 cells. The aim of the present study was to elucidate the anticancer effect of myricetin on human breast cancer MCF-7 cells and to explore the possible mechanisms of action. MCF-7 cells were treated with different concentrations of myricetin (0-80 µM) for 12, 24 and 48 h. In the present study, we found that myricetin suppressed the cell viability of the MCF-7 cells at least partly through the induction of apoptosis as determined by MTT assay and flow cytometry. Western blot analysis revealed that myricetin effectively suppressed the protein expression of p21-activated kinase 1 (PAK1), MEK and phosphorylated extracellular mitogen-activated protein kinase (ERK1/2). In addition, treatment of myricetin activated glycogen synthase kinase-3β (GSK3β) and Bax protein expression, and inhibited β-catenin/cyclin D1/proliferating cell nuclear antigen (PCNA)/survivin and promoted caspase-3 activity in the MCF-7 cells. These results demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells through PAK1/MEK/ERK/GSK3β/β-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling.

Introduction

Breast cancer is the most common malignant cancer among females. The highest morbidity occurs in northern America and northern European countries (1). Despite the fact that China is a country with low incidence, the morbidity is increasing year by year due to changes in dietary structures, living standards and life styles (2). According to new data, the morbidity of breast cancer is increasing yearly, and it is becoming a tumor with the highest death rates (3). Meanwhile, the age at onset is becoming increasingly younger (3).

p21-activated kinase 1 (PAK1) was first found as a member of the Pak family (4). Initially, it was cloned from cerebral tissues as p21 kinase (4). Members of the Pak family play an essential role in immune escape, motility, angiogenesis and genetic regulation (5). Therefore, the Pak family may constitute the critical node of signal transduction in the process of tumor progression. During the evolutionary process of colorectal malignant tumors, expression of Pak1 is increased. Recent studies have found that the activation of Pak1 is necessary for inducing lysophosphatidic acid and autotoxin in melanoma cells (6). In addition, Pak1 was found to be highly expressed in head and neck neoplasms (7).

As a key transmitter factor for the Wnt signal channel, β-catenin is expressed in many types of tumors (8). Its oncogenic potential in in vitro culture models and in vivo animal experiments have been extensively explored. The nuclear accumulation of β-catenin is generally considered as the symbol of Wnt/β-catenin signal routine. β-catenin accumulates and enters into the nucleus, which induces the expression of target genes (9).

Waxberry is a plant of the genus Myricaceae (10). Geographically, it is distributed between 18 and 33° north latitude while its economic cultivation is mainly distributed in southeast coast regions, such as Zhejiang, Jiangsu, Fujian, Guangdong and Jiangxi Provinces. Myricetin, found in the bark of waxberry, is bitter in taste and warm in property with antiviral, anti-inflammatory, antioxidant, free radical scavaging, immune adjustment, anti-androgenic and antiallergic functions (1113). In the present study, we examined the anticancer effects of myricetin. We found that myricetin suppressed the cell viability of human breast cancer MCF-7 cells. The mechanisms involved in the effects of myricetin were also investigated.

Materials and methods

Cell culture and cell viability

Human breast cancer MCF-7 cells were maintained in RPMI-1640 medium supplemented with 10% US-qualified fetal bovine serum (FBS) (both from Invitrogen, Grand Island, NY, USA) in a humidified incubator with 5% CO2 at 37°C. MCF-7 cells (1×104) were seeded into a 96-well plate, incubated at 37°C and then treated with different concentrations of myricetin (0–80 µM) for 12, 24 and 48 h. The medium was removed, and 50 µl MTT (5 mg/ml) was added to each well and then incubated at 37°C for 4 h. The supernatant was removed, and 200 µl of dimethyl sulfoxide (DMSO; Invitrogen) was dissolved for 20 min. Absorbance was measured at 490 nm.

Flow cytometric analysis of the apoptotic rate

MCF-7 cells (1×106) were seeded into a 6-well plate, incubated at 37°C, and then treated with different concentrations of myricetin (0, 10, 20 and 40 µM) for 24 h. MCF-7 cells were washed with cold phosphate-buffered saline (PBS) twice and re-suspended in binding buffer. Subsequently, 5 µl of FITC Annexin V and 1 µl propidium iodide (PI) were added to the cells and incubated for 20 min at room temperature in the dark. The apoptotic rate was determined by flow cytometry (FACSCalibur system; BD Biosciences, San Jose, CA, USA).

Western blot analysis

MCF-7 cells (1×106) were seeded into a 6-well plate, incubated at 37°C and then treated with different concentrations of myricetin (0, 10, 20 and 40 µM) for 24 h. MCF-7 cells were lysed in 100 µl mammalian protein extraction reagent (M-PER; Pierce, Rockford, IL, USA) and centrifuged at 7,500 × g for 15 min at 4°C. Total protein levels were determined by a BCA protein assay kit (Pierce). SDS-PAGE was performed using equivalent protein extracts (60 µg) from each sample, which were then blotted onto a nitrocellulose membrane using a Mini-Protean 3 system (Bio-Rad, Hercules, CA, USA). The blots were incubated in PBS containing 5% non-fat dry milk for 1 h. The membranes were incubated with the primary antibodies PAK1, MEK1/2, ERK1/2, GSK3β, β-catenin, cyclin D1, PCNA, survivin, Bax and β-actin at 4°C overnight. The membranes were then incubated with secondary antibody dilutions, washed with PBS containing 5% non-fat dry milk and visualized using enhanced chemiluminescence detection reagents (ECL Advance Western Blotting Detection kit; Amersham, UK).

Enzyme-linked immunosorbent assay (ELISA)

The MCF-7 cells (1×104) were seeded into a 96-well plate, incubated at 37°C and then treated with different concentrations of myricetin (0, 10, 20 and 40 µM) for 24 h. The caspase-3 assay kit (Ac-DEVD-pNA, 2 mM) was used to detect caspase-3 enzymatic activity in the MCF-7 cells. The absorbance was measured at 405 nm.

Statistical analysis

Data are expressed as mean ± standard error of the mean (SEM) and analyzed using ANOVA. The results were analyzed using a post hoc test (two-sided Dunnett's test) and one-way analysis of variance (ANOVA) to test differences between each treatment and the control. A p-value of <0.05 was considered to indicate a statistically significant result.

Results

Myricetin suppresses the cell viability of human breast cancer MCF-7 cells

The chemical structure of myricetin is shown in Fig. 1. MTT assay was performed to investigate the effect of myricetin on the viability of the MCF-7 cells following the treatment of myricetin. As shown in Fig. 2, myricetin suppressed the cell viability of the MCF-7 cells in a time- and dose-dependent manner. Particularly, the suppression of cell viability was evident after treatment with 80 µM of myricetin for 12 h, 20–80 µM of myricetin for 24 h and 10–80 µM of myricetin for 48 h (Fig. 2).

Myricetin induces the cell apoptosis of human breast cancer MCF-7 cells

Similarly, we examined the effect of myricetin on the cell apoptosis of MCF-7 cells using flow cytometric analysis. We observed that compared with the controls (myricetin 0 µM), 40 or 80 µM of myricetin significantly increased the apoptotic rate of the MCF-7 cells (Fig. 3).

Myricetin affects the PAK1 pathway in human breast cancer MCF-7 cells

In the MCF-7 models, we also examined whether myricetin affects the PAK1 pathway in MCF-7 cells. As shown in Fig. 4, myricetin (40 or 80 µM) significantly inhibited the protein expression of PAK1 in the MCF-7 cells when compared with the controls (myricetin 0 µM).

Myricetin affects the MEK1/2 pathway in human breast cancer MCF-7 cells

To ascertain whether myricetin affects the MEK1/2 pathway in MCF-7 cells, MEK1/2 protein expression was analyzed using western blot analysis. However, compared to the controls (myricetin 0 µM), treatment with 40 or 80 µM of myricetin significantly suppressed the MEK1/2 protein expression in the MCF-7 cells (Fig. 5).

Myricetin affects the ERK1/2 pathway in human breast cancer MCF-7 cells

Next, the role of the ERK1/2 pathway in myricetin-induced apoptosis was determined. p-ERK1/2 protein expression was determined in the MCF-7 cells. Treatment with 40 or 80 µM of myricetin significantly reduced the protein expression of p-ERK1/2 in the MCF-7 cells when compared with the controls (myricetin 0 µM) (Fig. 6).

Myricetin affects the GSK3β pathway in human breast cancer MCF-7 cells

GSK3β, a tumor-suppressor protein, was measured using western blot analysis. Compared to the controls (myricetin 0 µM), treatment with 40 or 80 µM of myricetin significantly activated the protein expression of GSK3β in the MCF-7 cells (Fig. 7).

Myricetin affects the β-catenin pathway in human breast cancer MCF-7 cells

Western blot analysis was used to investigate the role of the β-catenin pathway on myricetin-induced apoptosis in human breast cancer MCF-7 cells. As shown in Fig. 8, treatment with 40 or 80 µM of myricetin significantly suppressed the β-catenin protein expression in the MCF-7 cells when compared with the controls (myricetin 0 µM).

Myricetin affects the cyclin D1 pathway in human breast cancer MCF-7 cells

Western blot analysis was used to investigate the role of the cyclin D1 pathway in the myricetin-induced apoptosis in human breast cancer MCF-7 cells. As shown in Fig. 9 treatment with 40 or 80 µM of myricetin significantly inhibited the protein expression of cyclin D1 in the MCF-7 cells when compared with the controls (myricetin 0 µM).

Myricetin affects the PCNA pathway in human breast cancer MCF-7 cells

To further examine the effect of myricetin affected on the PCNA pathway of human breast cancer MCF-7 cells, PCNA protein expression in MCF-7 cells was detected using western blot analysis. As shown in Fig. 10, treatment with 40 or 80 µM of myricetin significantly suppressed the PCNA protein expression in MCF-7 cells when compared with the controls (myricetin 0 µM).

Myricetin affects the survivin pathway in human breast cancer MCF-7 cells

The survivin pathway induces apoptosis in cancer cells. Thus, we aimed to ascertain whether myricetin affects the survivin pathway in human breast cancer MCF-7 cells. As shown in Fig. 11, pretreatment with 40 or 80 µM of myricetin significantly inhibited the protein expression of survivin in the MCF-7 cells when compared with the controls (myricetin 0 µM).

Myricetin affects the Bax pathway in human breast cancer MCF-7 cells

To investigate whether the anticancer effect of myricetin on human breast cancer was caused by the Bax pathway, Bax protein expression of MCF-7 cells following treatment with myricetin was analyzed by western blot analysis. As shown in Fig. 12, treatment with 40 or 80 µM of myricetin significantly activated the protein expression of Bax in the MCF-7 cells when compared with the controls (myricetin 0 µM).

Myricetin affects the caspase-3 pathway in human breast cancer MCF-7 cells

Caspase-3 assay kit was used to confirm the mechanism involved in the anticancer effects of myricetin on the apoptosis in human breast cancer MCF-7 cells. Compared to the controls (myricetin 0 µM), myricetin (40 or 80 µM) significantly increased the caspase-3 activity in the MCF-7 cells (Fig. 13).

Discussion

As one of the most common malignant cancers, the morbidity of breast cancer is increasing worldwide. In China, owing to changes in life styles and dietary structures, the morbidity of breast cancer is increasing rapidly and its age at onset is becoming increasingly younger (2,14). Due to rapid progress and the wide application of molecular biology, research on the pathogenesis of cancer and its therapy has made substantial achievements (15). Our results found that myricetin suppressed the cell viability of human breast cancer MCF-7 cells at least partly through the induction of apoptosis.

Pak1 is pivotal to physiological processes such as normal cell movement, mitosis, transcription and interpretation (7). In head and neck neoplasms and sarcoma, the activities of Pak1 have been found to be higher than that in normal tissues (6). In the evolutionary process of colorectal malignant tumors, expression of Pak1 is increased (16). Studies have confirmed that Pak1 is closely associated with the invasion and metastasis of breast cancer, human oophoroma and prostate cancer, indicating the Pak1 plays an important role in normal tissue development and tumor progression (17,18). Pak1 was found to be related to cellular orientation movement while motility is rather important for tumor metastasis. It has been confirmed that Pak1 has definite functions in invasion and metastasis of breast cancers induced by HER2 (18,19). Further studies suggest that expression of Pak1 in breast cancer and its activities are positively related with tumor grade, and expression levels in poorly differentiated ductal carcinoma were higher than levels in higher differentiated ductal carcinoma (6). These results indicate that inhibition of the viability of MCF-7 cells following treatment with myricetin is through the PAK1 pathway. Iyer et al provide striking evidence that myricetin induces the apoptosis of hepatocellular carcinoma through inhibition of PAK1 signaling (11).

The frequency of the overexpression of MEK noted in breast cancer is 30% and is related with the poor prognosis and resistance to therapy (20). The overexpression of MEK can realize autonomous activation under conditions without extracellular ligands. This results in the occurrence of malignant tumors through the blocking of apoptosis induced by TNF (20). ERK can facilitate the proliferation of tumor cells. As an important signaling transduction pathway of MAPK, ERK can be activated by growth factors, serum, ligands of G-protein-coupled receptors and transcription factors (21). Growth factors can activate ERK through the phosphorylation of the Ras-Raf-MEK pathway. Firstly, growth factors bind with corresponding receptors on the cell surface and induce the phosphorylation of tyrosine residues on endochylema of receptors, resulting in dipolymers (22). Phosphorylated tyrosine residues can provide binding sites for proteins with SH2 structural domain (23). Expression of ERK in pancreatic cancer cells is significantly increased. It is known that the MEK/ERK signaling pathway triggers the dissociation and motility of pancreatic cancer cells and improves the invasion and metastasis of pancreatic cancer cells (24). The activation of the ERK signaling pathway can regulate the migratory abilities of tumor cells and facilitate the dissemination of tumor cells. These results indicate that myricetin induced apoptosis in the MCF-7 cells through the MEK/ERK signaling pathway. Lim et al found that myricetin upregulated cyclooxygenase-2 expression in mouse epidermal cells through the MEK/ERK signaling pathway (25).

The Wnt signaling pathway plays a pivotal role in cell growth, progression and differentiation. Aberrant expression of the Wnt pathway is the origin of many diseases (8). In regards to the classical Wnt/β-catenin pathway, when the Wnt signal is lost, β-catenin in the cytoplasm is at low levels, which can be degraded continuously by axin compounds (26). Axin compounds include scaffolding protein, casein kinase 1 and GSK3β. GSK3β can continuously phosphorylate amino terminal of β-catenin, resulting in the degradation of β-catenin by ubiquitin (27). When cells are stimulated, Wnt signals are activated. Wnt proteins combine with FZD proteins and low density lipoprotein receptor-related protein5/6. Dsh proteins are activated. GSK3β is phosphorylated, which can decrease the activity of GSK3β (24). Axin compound cannot trigger the phosphorylation and ubiquitylation of β-catenin, resulting in the accumulation of β-catenin. It combines with T cell transcription factor/lymphoid enhancer binding factors and activates the expression of cyclin D1, c-myc, MMp7, CD44, Bcl-2, VEGF and survivin (28). GSK3β can also activate the β-catenin signaling pathway and promote the occurrence of hyperplasia of the mammary glands (28). These results indicate that GSK3β/β-catenin/cyclin D1/PCNA/survivin-associated intrinsic pathways were, at least partly, involved in the myricetin-induced apoptosis of human breast cancer MCF-7 cells. Iyer et al provide striking evidence that myricetin induces the apoptosis of hepatocellular carcinoma through inhibition of GSK3β/β-catenin/cyclin D1/PCNA/survivin signaling (11).

Bcl-2 and Bax play an essential role in cell apoptosis. The sensitivity of cells to apoptosis-stimulating factors largely depends on the ratio of bcl-2 proteins/bax proteins. The proportion of bcl-2/bax in normal tissues is constant, which creates a balance for cell division and proliferation (29). During cell apoptosis, many proteins in the bcl-2 family play an important role in cell apoptosis. Therefore, the comprehensive expression levels of bcl-2 and bax are valuable for the occurrence, progression and prognosis of tumors (30). Our results demonstrated that myricetin inhibited the cell growth of MCF-7 cells through induction of Bax and caspase-3. Kim et al reported that myricetin induced apoptosis through the Bax/Bcl-2-dependent pathway in human colon cancer cells (10).

In conclusion, our data demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells at least partly through the induction of apoptosis. Our present results revealed that the anticancer effect of myricetin on human breast cancer involved PAK1/MEK/ERK/GSK3β/β-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling (Fig. 14). Thus, myricetin may be a new drug for the treatment of human breast cancer.

References

1 

Kida K, Ishikawa T, Yamada A, Shimizu D, Tanabe M, Sasaki T, Ichikawa Y and Endo I: A prospective feasibility study of sentinel node biopsy by modified Indigocarmine blue dye methods after neoadjuvant chemotherapy for breast cancer. Eur J Surg Oncol. 41:566–570. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Perez EA, Dueck AC, McCullough AE, Chen B, Geiger XJ, Jenkins RB, Lingle WL, Davidson NE, Martino S, Kaufman PA, et al: Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial. J Clin Oncol. 31:2115–2122. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Tang LC, Wang BY, Sun S, Zhang J, Jia Z, Lu YH, Di GH, Shao ZM and Hu XC: Higher rate of skin rash in a phase II trial with weekly nanoparticle albumin-bound paclitaxel and cisplatin combination in Chinese breast cancer patients. BMC Cancer. 13:2322013. View Article : Google Scholar : PubMed/NCBI

4 

Yoon JH, Mo JS, Ann EJ, Ahn JS, Jo EH, Lee HJ, Hong SH, Kim MY, Kim EG, Lee K, et al: NOTCH1 intracellular domain negatively regulates PAK1 signaling pathway through direct interaction. Biochim Biophys Acta. 1863:179–188. 2016. View Article : Google Scholar

5 

Khare V, Dammann K, Asboth M, Krnjic A, Jambrich M and Gasche C: Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer. Inflamm Bowel Dis. 21:287–296. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Nie J, Sun C, Faruque O, Ye G, Li J, Liang Q, Chang Z, Yang W, Han X and Shi Y: Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic β-cells. J Biol Chem. 287:26435–26444. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Chow HY, Jubb AM, Koch JN, Jaffer ZM, Stepanova D, Campbell DA, Duron SG, O'Farrell M, Cai KQ, Klein-Szanto AJ, et al: p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model. Cancer Res. 72:5966–5975. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Wang L, Tian H, Yuan J, Wu H, Wu J and Zhu X: CONSORT: Sam68 is directly regulated by miR-204 and promotes the self-renewal potential of breast cancer cells by activating the Wnt/beta-catenin signaling pathway. Medicine. 94:e22282015. View Article : Google Scholar : PubMed/NCBI

9 

Dong Y, Cao B, Zhang M, Han W, Herman JG, Fuks F, Zhao Y and Guo M: Epigenetic silencing of NKD2, a major component of Wnt signaling, promotes breast cancer growth. Oncotarget. 6:22126–22138. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Kim ME, Ha TK, Yoon JH and Lee JS: Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway. Anticancer Res. 34:701–706. 2014.PubMed/NCBI

11 

Iyer SC, Gopal A and Halagowder D: Myricetin induces apoptosis by inhibiting P21 activated kinase 1 (PAK1) signaling cascade in hepatocellular carcinoma. Mol Cell Biochem. 407:223–237. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Masuda T, Miura Y, Inai M and Masuda A: Enhancing effect of a cysteinyl thiol on the antioxidant activity of flavonoids and identification of the antioxidative thiol adducts of myricetin. Biosci Biotechnol Biochem. 77:1753–1758. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Kang KA, Wang ZH, Zhang R, Piao MJ, Kim KC, Kang SS, Kim YW, Lee J, Park D and Hyun JW: Myricetin protects cells against oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways. Int J Mol Sci. 11:4348–4360. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Arving C, Brandberg Y, Feldman I, Johansson B and Glimelius B: Cost-utility analysis of individual psychosocial support interventions for breast cancer patients in a randomized controlled study. Psychooncology. 23:251–258. 2014. View Article : Google Scholar

15 

Zhang J, Wang L, Wang Z, Hu X, Wang B, Cao J, Lv F, Zhen C, Zhang S and Shao Z: A phase II trial of biweekly vinorelbine and oxaliplatin in second- or third-line metastatic triple-negative breast cancer. Cancer Biol Ther. 16:225–232. 2015. View Article : Google Scholar : PubMed/NCBI

16 

DeSantiago J, Bare DJ, Xiao L, Ke Y, Solaro RJ and Banach K: p21-Activated kinase1 (Pak1) is a negative regulator of NADPH-oxidase 2 in ventricular myocytes. J Mol Cell Cardiol. 67:77–85. 2014. View Article : Google Scholar : PubMed/NCBI

17 

McDaniel AS, Allen JD, Park SJ, Jaffer ZM, Michels EG, Burgin SJ, Chen S, Bessler WK, Hofmann C, Ingram DA, et al: Pak1 regulates multiple c-kit mediated Ras-MAPK gain-in-function phenotypes in Nf1+/− masT cells. Blood. 112:4646–4654. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Holm C, Rayala S, Jirström K, Stål O, Kumar R and Landberg G: Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients. J Natl Cancer Inst. 98:671–680. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Smith SD, Jaffer ZM, Chernoff J and Ridley AJ: PAK1-mediated activation of ERK1/2 regulates lamellipodial dynamics. J Cell Sci. 121:3729–3736. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Dillon LM, Bean JR, Yang W, Shee K, Symonds LK, Balko JM, McDonald WH, Liu S, Gonzalez-Angulo AM, Mills GB, et al: P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT and MEK/ERK signaling in breast cancer. Oncogene. 34:3968–3976. 2015. View Article : Google Scholar

21 

Tarkkonen K, Ruohola J and Härkönen P: Fibroblast growth factor 8 induced downregulation of thrombospondin 1 is mediated by the MEK/ERK and PI3K pathways in breast cancer cells. Growth Factors. 28:256–267. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Liu WH, Liu HB, Gao DK, Ge GQ, Zhang P, Sun SR, Wang HM and Liu SB: ABCG2 protects kidney side population cells from hypoxia/reoxygenation injury through activation of the MEK/ERK pathway. Cell Transplant. 22:1859–1868. 2013. View Article : Google Scholar

23 

Navolanic PM, Lee JT and McCubrey JA: Docetaxel cytotoxicity is enhanced by inhibition of the Raf/MEK/ERK signal transduction pathway. Cancer Biol Ther. 2:677–678. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Li SQ, Wang ZH, Mi XG, Liu L and Tan Y: MiR-199a/b-3p suppresses migration and invasion of breast cancer cells by downregulating PAK4/MEK/ERK signaling pathway. IUBMB Life. 67:768–777. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Lim TG, Lee BK, Kwon JY, Jung SK and Lee KW: Acrylamide up-regulates cyclooxygenase-2 expression through the MEK/ERK signaling pathway in mouse epidermal cells. Food Chem Toxicol. 49:1249–1254. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Zhang J, Yang Z, Li P, Bledsoe G, Chao L and Chao J: Kallistatin antagonizes Wnt/β-catenin signaling and cancer cell motility via binding to low-density lipoprotein receptor-related protein 6. Mol Cell Biochem. 379:295–301. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Chow KH, Sun RW, Lam JB, Li CK, Xu A, Ma DL, Abagyan R, Wang Y and Che CM: A gold(III) porphyrin complex with antitumor properties targets the Wnt/beta-catenin pathway. Cancer Res. 70:329–337. 2010. View Article : Google Scholar

28 

Prasad CP, Chaurasiya SK, Axelsson L and Andersson T: WNT-5A triggers Cdc42 activation leading to an ERK1/2 dependent decrease in MMP9 activity and invasive migration of breast cancer cells. Mol Oncol. 7:870–883. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Zhu L, Zhu B, Yang L, Zhao X, Jiang H and Ma F: RelB regulates Bcl-xl expression and the irradiation-induced apoptosis of murine prostate cancer cells. Biomed Rep. 2:354–358. 2014.PubMed/NCBI

30 

Guo Y, Zhang Y, Yang X, Lu P, Yan X, Xiao F, Zhou H, Wen C, Shi M, Lu J, et al: Effects of methylglyoxal and glyoxalase I inhibition on breast Cancer cells proliferation, invasion, and apoptosis through modulation of MAPKs, MMP9, and Bcl-2. Cancer Biol Ther. 1–12. 2015.

Related Articles

Journal Cover

July-2016
Volume 36 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Jiao D and Jiao D: Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway. Oncol Rep 36: 342-348, 2016
APA
Jiao, D., & Jiao, D. (2016). Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway. Oncology Reports, 36, 342-348. https://doi.org/10.3892/or.2016.4777
MLA
Jiao, D., Zhang, X. D."Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway". Oncology Reports 36.1 (2016): 342-348.
Chicago
Jiao, D., Zhang, X. D."Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway". Oncology Reports 36, no. 1 (2016): 342-348. https://doi.org/10.3892/or.2016.4777