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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Research Article

Scutellarin Suppressed Proliferation and Induced Apoptosis in Gastric Cancer via Wnt/β-catenin Signaling Pathway

Author(s): Zhenkai Wang, Xiang Liu, Wanzhen Chen, Xiujun Guo, Lili Chen, Zhiqin Wei, Dan Liu and Zheng Liu*

Volume 29, Issue 5, 2023

Published on: 14 February, 2023

Page: [368 - 378] Pages: 11

DOI: 10.2174/1381612829666230130141931

Price: $65

Abstract

Background: Scutellarin exerts anticancer effects on diverse malignancies. However, its function in gastric cancer has not been explored.

Objective: This study aimed to examine the anticancer effect and molecular mechanism of scutellarin in gastric cancer.

Materials and Methods: Gastric cancer cells were treated with scutellarin and transfected with the Wnt1 overexpression plasmid. Cell viability, proliferation, toxicity, and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation, lactate dehydrogenase (LDH) activity, TdT-mediated dUTP Nick-End Labeling (TUNEL), and flow cytometry assays. Expressions of apoptosis-related and Wnt/β-catenin signaling pathway- related proteins were examined by western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: Scutellarin concentration dependently restrained cell viability. Scutellarin (20 and 80 μmol/L) suppressed proliferation and promoted LDH release and apoptosis. Moreover, scutellarin elevated Bax and Cytochrome C levels but diminished the levels of Bcl-2, Wnt1, cytoplasmic β-catenin, and basal cytoplasmic β- catenin. However, the above-mentioned regulatory effects of scutellarin were all reversed by Wnt1 overexpression.

Conclusion: Scutellarin suppressed gastric cancer cell proliferation and promoted apoptosis by inhibition of the Wnt/β-catenin pathway.

Keywords: Scutellarin, gastric cancer, apoptosis, Wnt/β-catenin signaling pathway, radiotherapy, chemotherapy.

« Previous Next »
[1]
Smyth EC, Nilsson M, Grabsch HI, van Grieken NCT, Lordick F. Gastric cancer. Lancet 2020; 396(10251): 635-48.
[http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]
[2]
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: Descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev 2014; 23(5): 700-13.
[http://dx.doi.org/10.1158/1055-9965.EPI-13-1057] [PMID: 24618998]
[3]
Johnston FM, Beckman M. Updates on management of gastric cancer. Curr Oncol Rep 2019; 21(8): 67.
[http://dx.doi.org/10.1007/s11912-019-0820-4] [PMID: 31236716]
[4]
Tan Z. Recent advances in the surgical treatment of advanced gastric cancer: A review. Med Sci Monit 2019; 25: 3537-41.
[http://dx.doi.org/10.12659/MSM.916475] [PMID: 31080234]
[5]
Hung KF, Hsu CP, Chiang JH, et al. Complementary Chinese herbal medicine therapy improves survival of patients with gastric cancer in Taiwan: A nationwide retrospective matched-cohort study. J Ethnopharmacol 2017; 199: 168-74.
[http://dx.doi.org/10.1016/j.jep.2017.02.004] [PMID: 28163114]
[6]
Yang J, Zhu L, Wu Z, Wang Y. Chinese herbal medicines for induction of remission in advanced or late gastric cancer. Cochrane Libr 2013; (4): CD005096.
[http://dx.doi.org/10.1002/14651858.CD005096.pub4] [PMID: 23633324]
[7]
Yu F, Takahashi T, Moriya J, et al. Traditional Chinese medicine and Kampo: A review from the distant past for the future. J Int Med Res 2006; 34(3): 231-9.
[http://dx.doi.org/10.1177/147323000603400301] [PMID: 16866016]
[8]
Xiang Y, Guo Z, Zhu P, Chen J, Huang Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med 2019; 8(5): 1958-75.
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[9]
Qi F, Zhao L, Zhou A, et al. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends 2015; 9(1): 16-34.
[http://dx.doi.org/10.5582/bst.2015.01019] [PMID: 25787906]
[10]
Guo D, Zhang W, Yang H, et al. Celastrol induces necroptosis and ameliorates inflammation via targeting biglycan in human gastric carcinoma. Int J Mol Sci 2019; 20(22): 5716.
[http://dx.doi.org/10.3390/ijms20225716] [PMID: 31739592]
[11]
Zhou Y, Xu Q, Shang J, Lu L, Chen G. Crocin inhibits the migration, invasion, and epithelial-mesenchymal transition of gastric cancer cells via miR-320/KLF5/HIF-1α signaling. J Cell Physiol 2019; 234(10): 17876-85.
[http://dx.doi.org/10.1002/jcp.28418] [PMID: 30851060]
[12]
Zhao T, Tang H, Xie L, et al. Scutellaria baicalensis Georgi. (Lamiaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol 2019; 71(9): 1353-69.
[http://dx.doi.org/10.1111/jphp.13129] [PMID: 31236960]
[13]
Sun C, Li C, Li X, et al. Scutellarin induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT signaling pathways in vitro and in vivo. J Cancer 2018; 9(18): 3247-56.
[http://dx.doi.org/10.7150/jca.25921] [PMID: 30271483]
[14]
Xie Z, Guo Z, Lei J, Yu J. Scutellarin synergistically enhances cisplatin effect against ovarian cancer cells through enhancing the ability of cisplatin binding to DNA. Eur J Pharmacol 2019; 844: 9-16.
[http://dx.doi.org/10.1016/j.ejphar.2018.11.040] [PMID: 30503360]
[15]
Liu K, Tian T, Zheng Y, et al. Scutellarin inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of JAK2/STAT3 pathway. J Cell Mol Med 2019; 23(4): 3040-4.
[http://dx.doi.org/10.1111/jcmm.14169] [PMID: 30697962]
[16]
Hou L, Chen L, Fang L. Scutellarin inhibits proliferation, invasion, and tumorigenicity in human breast cancer cells by regulating HIPPO-YAP signaling pathway. Med Sci Monit 2017; 23: 5130-8.
[http://dx.doi.org/10.12659/MSM.904492] [PMID: 29079722]
[17]
Bao J, Xia L, Zhao Y, Xia R. Scutellarin exerts anticancer effects on human leukemia cells via induction of Sub-G1 cell cycle arrest, apoptosis and also inhibits migration and invasion by targeting Raf/MEK/ERK signalling pathway. J BUON 2020; 25(2): 1050-5.
[PMID: 32521905]
[18]
Zhu PT, Mao M, Liu ZG, Tao L, Yan BC. Scutellarin suppresses human colorectal cancer metastasis and angiogenesis by targeting ephrinb2. Am J Transl Res 2017; 9(11): 5094-104.
[PMID: 29218107]
[19]
Barranco SC, Townsend CM Jr, Casartelli C, et al. Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Res 1983; 43(4): 1703-9.
[PMID: 6831414]
[20]
Akagi T, Kimoto T. Human cell line (HGC-27) derived from the metastatic lymph node of gastric cancer. Acta Med Okayama 1976; 30(3): 215-9.
[PMID: 136873]
[21]
Ke Y, Ning T, Wang B. Establishment and characterization of a SV40 transformed human fetal gastric epithelial cell line-GES-1. Zhonghua Zhong Liu Za Zhi 1994; 16(1): 7-10.
[PMID: 8033753]
[22]
Alegria-Schaffer A, Lodge A, Vattem K. Chapter 33 performing and optimizing western blots with an emphasis on chemiluminescent detection. Guide to Protein Purification. (2nd Edition.). 2009; pp. 573-99.
[23]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(delta delta C(T)) method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[24]
Venkatarame Gowda Saralamma V, Lee HJ, Hong GE, et al. Korean Scutellaria baicalensis Georgi flavonoid extract induces mitochondrially mediated apoptosis in human gastric cancer AGS cells. Oncol Lett 2017; 14(1): 607-14.
[http://dx.doi.org/10.3892/ol.2017.6184] [PMID: 28693212]
[25]
Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the lactate dehydrogenase assay. Cold Spring Harb Protoc 2018; 2018
[http://dx.doi.org/10.1101/pdb.prot095497]
[26]
McArthur K, Whitehead LW, Heddleston JM, et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science 2018; 359(6378): eaao6047.
[http://dx.doi.org/10.1126/science.aao6047] [PMID: 29472455]
[27]
Hao Z, Duncan GS, Chang CC, et al. Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell 2005; 121(4): 579-91.
[http://dx.doi.org/10.1016/j.cell.2005.03.016] [PMID: 15907471]
[28]
Taylor RC, Cullen SP, Martin SJ. Apoptosis: Controlled demolition at the cellular level. Nat Rev Mol Cell Biol 2008; 9(3): 231-41.
[http://dx.doi.org/10.1038/nrm2312] [PMID: 18073771]
[29]
Grebennikova TA, Belaya ZE, Rozhinskaya LY, Melnichenko GA. The canonical Wnt/β-catenin pathway: From the history of its discovery to clinical application. Ter Arkh 2016; 88(10): 74-81.
[http://dx.doi.org/10.17116/terarkh201688674-81] [PMID: 28635854]
[30]
Pai SG, Carneiro BA, Mota JM, et al. Wnt/beta-catenin pathway: Modulating anticancer immune response. J Hematol Oncol 2017; 10(1): 101.
[http://dx.doi.org/10.1186/s13045-017-0471-6] [PMID: 28476164]
[31]
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene 2017; 36(11): 1461-73.
[http://dx.doi.org/10.1038/onc.2016.304] [PMID: 27617575]
[32]
Chen X, Duan N, Zhang C, Zhang W. Survivin and tumorigenesis: Molecular mechanisms and therapeutic strategies. J Cancer 2016; 7(3): 314-23.
[http://dx.doi.org/10.7150/jca.13332] [PMID: 26918045]
[33]
Thakur R, Mishra DP. Pharmacological modulation of beta- catenin and its applications in cancer therapy. J Cell Mol Med 2013; 17(4): 449-56.
[http://dx.doi.org/10.1111/jcmm.12033] [PMID: 23490077]
[34]
Li LF, Wei ZJ, Sun H, Jiang B. Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis. World J Gastroenterol 2014; 20(34): 12313-21.
[http://dx.doi.org/10.3748/wjg.v20.i34.12313] [PMID: 25232267]
[35]
Mao J, Fan S, Ma W, et al. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis 2014; 5(1): e1039.
[http://dx.doi.org/10.1038/cddis.2013.515] [PMID: 24481453]
[36]
Liu F, Li L, Lu W, et al. Scutellarin ameliorates cartilage degeneration in osteoarthritis by inhibiting the Wnt/β-catenin and MAPK signaling pathways. Int Immunopharmacol 2020; 78: 105954.
[http://dx.doi.org/10.1016/j.intimp.2019.105954] [PMID: 31757676]
[37]
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917): 860-7.
[http://dx.doi.org/10.1038/nature01322] [PMID: 12490959]
[38]
Lynch HT, Grady W, Suriano G, Huntsman D. Gastric cancer: New genetic developments. J Surg Oncol 2005; 90(3): 114-33.
[http://dx.doi.org/10.1002/jso.20214] [PMID: 15895459]
[39]
Ju SH, Tan LR, Liu PW, et al. Scutellarin regulates osteoarthritis in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway. Mol Med Rep 2021; 23(1): 23.
[PMID: 33236146]
[40]
Xu L, Chen R, Zhang X, et al. Scutellarin protects against diabetic cardiomyopathy via inhibiting oxidative stress and inflammatory response in mice. Ann Palliat Med 2021; 10(3): 2481-93.
[http://dx.doi.org/10.21037/apm-19-516] [PMID: 33549002]
[41]
Zhang Y, Zhang Z, Wang J, et al. Scutellarin alleviates cerebral ischemia/reperfusion by suppressing oxidative stress and inflammatory responses viaMAPK/NF-κB pathways in rats. Environ Toxicol 2022; 37(12): 2889-96.
[http://dx.doi.org/10.1002/tox.23645] [PMID: 36036213]
[42]
Rihawi K, Ricci AD, Rizzo A, et al. Tumor-associated macrophages and inflammatory microenvironment in gastric cancer: Novel translational implications. Int J Mol Sci 2021; 22(8): 3805.
[http://dx.doi.org/10.3390/ijms22083805] [PMID: 33916915]
[43]
Sun J, Meng M. Chemoprotective effect of scutellarin against gastric cancer in rats: An in vitro and in vivo study. J Oleo Sci 2022; 71(7): 1003-12.
[http://dx.doi.org/10.5650/jos.ess21399] [PMID: 35781253]

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