AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Food Science and Human Wellness Article
PDF (8.2 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Open Access

Mechanism of action of cordycepin in the treatment of hepatocellular carcinoma via regulation of the Hippo signaling pathway

Xiaomin Li,, Qing Liu, Songyu Xie, Xiaoping Wu, Junsheng Fu( )
College of Life Sciences, Mycological Research Center, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Peer review under responsibility of Tsinghua University Press.

Show Author Information

Abstract

Hepatocellular carcinoma (HCC) is one of the common most malignant tumors. This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action. The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis. Transcriptome sequencing analysis revealed a total of 403 differential genes, which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway. The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor. The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1, and subsequently inhibited YAP1, which activated the Hippo signaling pathway. This in turn downregulated the expression of GBP3 and ETV5, and subsequently inhibited cell proliferation and migration. Additionally, YAP1 regulated the expression of Bax and Bcl-2, regulated the mitochondrial apoptotic pathway, and induced apoptosis by upregulating the expression of the caspase-3 protein. In summary, this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway, and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.

Keywords

Hepatocellular carcinomaCordycepinHippo signaling pathwayGBP3ETV5

Electronic Supplementary Material

Download File(s)
fshw-13-2-1040_ESM.docx (23.1 KB)

References

[1]

M.M Cao, H. Li, D.Q Sun, et al., Global epidemiology of liver cancer in 2020, Chinese J. Cancer Prev. Treat. 29(5) (2022) 322-328. https://doi.org/10.16073/j.cnki.cjcpt.2022.05.03.
Crossref Google Scholar
[2]

N. Zhang, S.H Bai, F.H Zhang, et al., Molecular markers and mechanisms for stemness maintenance of liver cancer stem cells: a review, Sheng Wu Gong Cheng Xue Bao 37(8) (2021) 2719-2736. http://doi.org/10.13345/j.cjb.200549.
Crossref Google Scholar
[3]

H.R Tang, Y.X Han, X.J Liu, Research progress on the pharmacological effects of Cordyceps militaris polysaccharide and adenosine, Biochem. Eng. J. 8(1) (2022) 164-167.
Google Scholar
[4]

Z. Wang, Z. Chen, Z. Jiang, et al., Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, Nat. Commun. 10(1) (2019) 2538. http://doi.org/10.1038/s41467-019-10386-8.
Crossref Google Scholar
[5]

T. Zaid, J. Helena, X. Yang, The Hippo pathway: immunity and cancer, Cancers 10(4) (2018) 94. http://doi.org/10.3390/cancers10040094.
Crossref Google Scholar
[6]

M.Z Wang, Y. Zhou, K.T He, et al., Research progress on the mechanism of Hippo pathway in tumorigenesis and development, J. Modern Oncol. 30(16) (2022) 3061-3064.
Crossref Google Scholar
[7]

C.G Hansen, T. Moroishi, K.L Guan, YAP and TAZ: a nexus for Hippo signaling and beyond, Trends Cell Biol. (2015) 499-513. http://doi.org/10.1016/j.tcb.2015.05.002.
Crossref Google Scholar
[8]

K. Brodowska, A. Al-Moujahed, A. Marmalidou, et al., The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation, Exp. Eye Res. 124(8) (2014) 67-73. http://doi.org/10.1016/j.exer.2014.04.011.
Crossref Google Scholar
[9]

K. Cui, W.W Wu, Q.Y Diao, Application and research progress on transcriptomics, Biotechnol. Bull. 35 (2019) 1-9.
Crossref Google Scholar
[10]

R. Zhou, J.H Gao, F.F Guo, et al., Analysis of crucial transcription factors of Berberine against cerebral ischemia based on transcriptomics and proteomics, Chinese Journal of Experimental Traditional Medical Formulae. (2021) 1. https://doi.org/10.13422/j.cnki.syfjx.20211849.
Crossref Google Scholar
[11]

M. Kanehisa, S. Goto, S. Kawashima, et al., The KEGG resource for deciphering the genome. Nucleic Acids Res. 32 (2004) D277-D280. http://doi.org/10.1093/nar/gkh063.
Crossref Google Scholar
[12]

A.M Liu, M.Z Xu, J.F Chen, et al., Targeting YAP and Hippo signaling pathway in liver cancer, Expert Opin. Ther. Tar. 14(8) (2010) 855. http://doi.org/10.1517/14728222.2010.499361.
Crossref Google Scholar
[13]

D.W Zhou, C. Conrad, F. Xia, et al., Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene, Cancer Cell. 16(5) (2009) 425-438. http://doi.org/10.1016/j.ccr.2009.09.026.
Crossref Google Scholar
[14]

S.Y Luo, K.Y Sit, A.D Sihoe, et al., Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas, Lung Cancer 85(2) (2014) 282-292. http://doi.org/10.1016/j.lungcan.2014.05.025.
Crossref Google Scholar
[15]

H. Xu, L.L Sun, Y.W Zheng, et al., GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis, Biochem. Biophys. Res. Commun. 495(1) (2018) 446-453. http://doi.org/10.1016/j.bbrc.2017.11.050.
Crossref Google Scholar
[16]

H. Xu, J. Jin, Y. Chen, et al., GBP3 promotes glioblastoma resistance to temozolomide by enhancing DNA damage repair, Oncogene 41(31) (2022) 3876-3885. http://doi.org/10.1038/s41388-022-02397-5.
Crossref Google Scholar
[17]

D. Meng, Z. Li, X. Ma, et al., ETV5 overexpression contributes to tumor growth and progression of thyroid cancer through PIK3CA, Life Sci. 253 (2020) 117693. http://doi.org/10.1016/j.lfs.2020.117693.
Crossref Google Scholar
[18]

S.J Jin, K.P Guo, Y.N Huang, et al., Protective effects of disodium guanylate on mice with acute liver injury induced by LPS/D-GalN via inhibiting the Caspase 3/Bax/BcI-2 signaling pathway, Modern Preventive Medicine 48(23) (2021) 4365-4369;4402.
Google Scholar
[19]

P.D Li, Y.H Wang, Y. Xiao, et al., Effects of hydroquinone on apoptosis and expression of Bcl-2, Bax and Caspase-3 in human leukemia cells, Modern Preventive Medicine 45(5) (2018) 878-882.
Google Scholar
[20]

R. Yu, J.Y Wang, D.T Tao, et al., Resveratrol regulating mitochondrial pathway to induce apoptosis of oral squamous cell carcinoma cells, Journal of Wannan Medical College 41(2) (2022) 161-165.
Google Scholar
[21]

N. Volkmann, F.M Marassi, D.D Newmeyer et al., The rheostat in the membrane: BCL-2 family proteins and apoptosis. Cell Death Differ. 21(2) (2014) 206-215. http://doi.org/10.1038/cdd.2013.153.
Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 2,
March 2024
Pages 1040-1054
DOI: 10.26599/FSHW.2022.9250090
Cite this article:
Li X, Liu Q, Xie S, et al. Mechanism of action of cordycepin in the treatment of hepatocellular carcinoma via regulation of the Hippo signaling pathway. Food Science and Human Wellness, 2024, 13(2): 1040-1054. https://doi.org/10.26599/FSHW.2022.9250090

1164

Views

146

Downloads

2

Crossref

1

Web of Science

1

Scopus

0

CSCD

Altmetrics
Received: 08 September 2022
Revised: 22 September 2022
Accepted: 21 October 2022
Published: 25 September 2023
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return