Abstract
Purpose
β-asarone is the prime component of essential oil extracted from Acori graminei Rhizoma, which plays an inhibitory role in various tumors. Here, we aim to investigate the functions as well as the mechanism of β-asarone in retinoblastoma (RB).
Methods
RB cell lines SO-Rb50 and HXO-Rb44 were treated with different doses of β-asarone. Then, CCK8 and BrdU experiments were adopted to examine the RB cell proliferation. Wound healing test and Transwell assay were employed to detect cell migration and invasion. RB cell apoptosis was tested by flow cytometry and Western blot. An RB cell xenograft model was constructed on nude mice for testing the role of β-asarone on RB cell growth in vivo. RT-PCR and Western blot were used to determine the effect of β-asarone on Wnt/β-catenin signaling pathway. Furthermore, the Wnt/β-catenin pathway inhibitor PNU-74654 and activator HLY78 were administered to RB cells for confirming the effects of β-asarone in Wnt/β-catenin pathway.
Results
In vivo experiment showed that β-asarone attenuated SO-Rb50 cell growth in nude mice. Further research found that β-asarone significantly repressed Wnt/β-catenin canonical pathway activation.
Conclusion
Prior inhibition of Wnt/β-catenin pathway abolished the antitumor effects induced by β-asarone. β-asarone exerted antitumor effects in RB cells by inactivating the Wnt/β-catenin signaling pathway.
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Availability of data and materials
The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- RB:
-
Retinoblastoma
- ERK:
-
Extracellular signal-regulated kinase
- AD:
-
Alzheimer's disease
- MAT:
-
Matrine
- KIF18B:
-
Kinesin family member 18B
- DMSO:
-
Dimethylsulfoxide
- CCK8:
-
Cell Counting Kit 8
- OD:
-
Optical density
- BrdU:
-
Bromo-2′-deoxyuridine
- DAPI:
-
Dianmidino-2-phenylindole
- LiCl:
-
Lithium chloride
References
Shah PK, Sripriya S, Narendran V, Pandian AJ (2016) Prenatal genetic diagnosis of retinoblastoma and report of RB1 gene mutation from India. Ophthalmic Genet 37(4):430–433
Rao R, Honavar SG (2017) Retinoblastoma. Indian J Pediatr 84(12):937–944
Pritchard EM, Dyer MA, Guy RK (2016) Progress in Small Molecule therapeutics for the treatment of retinoblastoma. Mini Rev Med Chem 16(6):430–454
Liu L, Wang J, Shi L, Zhang W, Du X, Wang Z, Zhang Y (2013) β-Asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression. Phytomedicine 20(6):512–520
Dong H, Cong W, Guo X, Wang Y, Tong S, Li Q, Li C (2019) β-asarone relieves chronic unpredictable mild stress induced depression by regulating the extracellular signal-regulated kinase signaling pathway. Exp Ther Med 18(5):3767–3774
Chang W, Teng J (2018) Combined application of tenuigenin and β-asarone improved the efficacy of memantine in treating moderate-to-severe Alzheimer’s disease. Drug Des Devel Ther 12:455–462
Lv LN, Wang XC, Tao LJ, Li HW, Li SY, Zheng FM (2019) β-Asarone increases doxorubicin sensitivity by suppressing NF-κB signaling and abolishes doxorubicin-induced enrichment of stem-like population by destabilizing Bmi1. Cancer Cell Int 19:153
Li L, Yang Y, Wu M, Yu Z, Wang C, Dou G, He H, Wang H, Yang N, Qi H, Xu X (2018) β-Asarone induces apoptosis and cell cycle arrest of human glioma U251 cells via suppression of HnRNP A2/B1-mediated pathway in vitro and In vivo. Molecules 23(5):1072
Silva-García O, Valdez-Alarcón JJ, Baizabal-Aguirre VM (2014) The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria. Mediators Inflamm 2014:310183
Lv Z, Wang C, Yuan T, Liu Y, Song T, Liu Y, Chen C, Yang M, Tang Z, Shi Q, Weng Y (2014) Bone morphogenetic protein 9 regulates tumor growth of osteosarcoma cells through the Wnt/β-catenin pathway. Oncol Rep 31(2):989–994
Liu J, Guo Y, Cao J (2020) Matrine triggers colon cancer cell apoptosis and G0/G1 cell cycle arrest via mediation of microRNA-22. Phytother Res 34(7):1619–1628
Yang B, Wang S, Xie H, Wang C, Gao X, Rong Y, Liu Z, Lu Y (2020) KIF18B promotes hepatocellular carcinoma progression through activating Wnt/β-catenin-signaling pathway. J Cell Physiol 235(10):6507–6514
Jiang Y, Wang W, Wu X, Shi J (2020) Pizotifen inhibits the proliferation and invasion of gastric cancer cells. Exp Ther Med 19(2):817–824
He H, Qin M (2020) Long non-coding RNA LEF1-AS1 is involved in the progression of retinoblastoma through regulating the Wnt/β-catenin pathway. Clin Exp Pharmacol Physiol 47(5):886–891
Wu T, Wang LN, Tang DR, Sun FY (2017) SOST silencing promotes proliferation and invasion and reduces apoptosis of retinoblastoma cells by activating Wnt/β-catenin signaling pathway. Gene Ther 24(7):399–407
Berry JL, Polski A, Cavenee WK, Dryja TP, Murphree AL, Gallie BL (2019) The RB1 story: characterization and cloning of the first tumor suppressor gene. Genes (Basel) 10(11):879
Fabian ID, Johnson KP, Stacey AW, Sagoo MS, Reddy MA (2017) Focal laser treatment in addition to chemotherapy for retinoblastoma. Cochrane Database Syst Rev. 6(6):012366–1111
Wang N, Zhang Q, Luo L, Ning B, Fang Y (2018) β-asarone inhibited cell growth and promoted autophagy via P53/Bcl-2/Bclin-1 and P53/AMPK/mTOR pathways in Human Glioma U251 cells. J Cell Physiol 233(3):2434–2443
Yooboon T, Kuramitsu K, Bullangpoti V, Kainoh Y, Furukawa S (2019) Cytotoxic effects of β-asarone on Sf9 insect cells. Arch Insect Biochem Physiol 02(1):e21596
Yang QQ, Xue WZ, Zou RX, Xu Y, Du Y, Wang S, Xu L, Chen YZ, Wang HL, Chen XT (2016) β-Asarone Rescues Pb-Induced Impairments of Spatial Memory and Synaptogenesis in Rats. PLoS ONE 11(12):e0167401
Yang Y, Xuan L, Chen H, Dai S, Ji L, Bao Y, Li C (2017) Neuroprotective Effects and Mechanism of β-Asarone against Aβ1-42-Induced Injury in Astrocytes. Evid Based Complement Alternat Med 2017:8516518
Li L, Wu M, Wang C, Yu Z, Wang H, Qi H, Xu X (2018) β-Asarone Inhibits Invasion and EMT in Human Glioma U251 Cells by Suppressing Splicing Factor HnRNP A2/B1. Molecules 23(3):671
Wang TL, Ouyang CS, Lin LZ (2018) β-asarone suppresses Wnt/β-catenin signaling to reduce viability, inhibit migration/invasion/adhesion and induce mitochondria-related apoptosis in lung cancer cells. Biomed Pharmacother 106:821–830
Wang N, Han Y, Luo L, Zhang Q, Ning B, Fang Y (2018) β-asarone induces cell apoptosis, inhibits cell proliferation and decreases migration and invasion of glioma cells. Biomed Pharmacother 106:655–664
Wu J, Zhang XX, Sun QM, Chen M, Liu SL, Zhang X, Zhou JY, Zou X (2015) β-Asarone inhibits gastric cancer cell proliferation. Oncol Rep 34(6):3043–3050
Shang S, Hua F, Hu ZW (2017) The regulation of β-catenin activity and function in cancer: therapeutic opportunities. Oncotarget 8(20):33972–33989
Valenta T, Hausmann G, Basler K (2012) The many faces and functions of β-catenin. EMBO J 31(12):2714–2736
Steinhart Z, Angers S (2018) Wnt signaling in development and tissue homeostasis. Development. https://doi.org/10.1242/dev.146589
Deng S, Zhang X, Qin Y, Chen W, Fan H, Feng X, Wang J, Yan R, Zhao Y, Cheng Y, Wei Y, Fan X, Ashktorab H, Smoot D, Meltzer SJ, Li S, Li K, Peng Y, Jin Z (2020) miRNA-192 and -215 activate Wnt/β-catenin signaling pathway in gastric cancer via APC. J Cell Physiol 235(9):6218–6229
Li Z, Li Q, Wang G, Huang Y, Mao X, Zhang Y, Wang X (2017) Inhibition of Wnt/β-catenin by anthelmintic drug niclosamide effectively targets growth, survival, and angiogenesis of retinoblastoma. Am J Transl Res 9(8):3776–3786
Silva AK, Yi H, Hayes SH, Seigel GM, Hackam AS (2010) Lithium chloride regulates the proliferation of stem-like cells in retinoblastoma cell lines: a potential role for the canonical Wnt signaling pathway. Mol Vis 16:36–45
Zhang Y, Chen H, Li W, Zhu Y (2014) Antiproliferative and apoptotic effects of indomethacin on human retinoblastoma cell line Y79 and the involvement of β-catenin, nuclear factor-κB and Akt signaling pathways. Ophthalmic Res 51(2):109–115
Wang X, Xu C, Hua Y, Cheng K, Zhang Y, Liu J, Han Y, Liu S, Zhang G, Xu S, Yang Z (2018) Psoralen induced cell cycle arrest by modulating Wnt/β-catenin pathway in breast cancer cells. Sci Rep 8(1):14001
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This study was supported by Fund of Xi’an Science and Technology Bureau (20YXYJ0008(2)).
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SB and JS conceived and designed the experiments; SB, FL and FL performed the experiments; Statistical analysis was contributed by FL and CB; CB wrote the paper. All authors read and approved the final manuscript.
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Bai, S., Shao, J., Bi, C. et al. β-asarone attenuates the proliferation, migration and enhances apoptosis of retinoblastoma through Wnt/β-catenin signaling pathway. Int Ophthalmol 43, 1687–1699 (2023). https://doi.org/10.1007/s10792-022-02566-1
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DOI: https://doi.org/10.1007/s10792-022-02566-1