Cordycepin Inhibits Human Gestational Choriocarcinoma Cell Growth by Disrupting Centrosome Homeostasis

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2020 Aug 18

PMID 32801639

Citations 6

Authors

Chia-Yih Wang

Shih-Wei Tsai

Han-Hsiang Chien

Ting-Yu Chen

Shi-Yuan Sheu

Edmund Cheung So

Bu-Miin Huang

Affiliations

Soon will be listed here.

Abstract

Introduction: Human gestational choriocarcinoma, a type of gestational trophoblastic disease, occurs after miscarriage, abortion, ectopic pregnancy, or molar pregnancy. Despite recent advances in the mechanism of anticancer drugs that induce human gestational choriocarcinoma apoptosis or block its growth, new therapeutic approaches are needed to be established. Cordycepin is an active anti-cancer component extracted from . It prevents cell proliferation both in vitro and in vivo.

Materials And Methods: Here, we examined cell growth by counting cell numbers, and performing a flow cytometry assay and EdU incorporation assay. Centrosome and cytoskeleton-related structures were observed by immunofluorescence assay. The DNA damage-related signaling was examined by Western blot assay.

Results: Here, we showed that cordycepin inhibited human gestational choriocarcinoma cell proliferation and induced cell death. In addition, treatment with cordycepin activated DNA-PK and ERK, thus inducing centrosome amplification and aberrant mitosis. These amplified centrosomes also disrupted microtubule arrays and actin networks, thus leading to defective cell adhesion. Furthermore, cordycepin induced autophagy for triggering cell death.

Conclusion: Thus, our study demonstrates that cordycepin inhibits cell proliferation and disrupts the cytoskeleton by triggering centrosome amplification.

Citing Articles

Treatment with autophagic inhibitors enhances oligonol‑induced apoptotic effects in nasopharyngeal carcinoma cells.

Wu Y, Lin C, Chiu W, Hsieh T, Chang S, Chang Y Biomed Rep. 2024; 21(4):143.

PMID: 39161943 PMC: 11332131. DOI: 10.3892/br.2024.1831.

Application and research progress of cordycepin in the treatment of tumours (Review).

He R, Zhou W Mol Med Rep. 2024; 30(3).

PMID: 38994776 PMC: 11258602. DOI: 10.3892/mmr.2024.13285.

Structural and pharmacological insights into cordycepin for neoplasms and metabolic disorders.

Zhang J, Yang Z, Zhao Z, Zhang N Front Pharmacol. 2024; 15:1367820.

PMID: 38953102 PMC: 11215060. DOI: 10.3389/fphar.2024.1367820.

Cordycepin Suppresses The Malignant Phenotypes of Colon Cancer Cells through The GSK3ß/ß-catenin/cyclin D1 Signaling Pathway.

Xu J, Shen X, Sun D, Zhu Y Cell J. 2022; 24(5):255-260.

PMID: 35717567 PMC: 9445518. DOI: 10.22074/cellj.2022.8160.

A Systematic Review of the Biological Effects of Cordycepin.

Radhi M, Ashraf S, Lawrence S, Tranholm A, Wellham P, Hafeez A Molecules. 2021; 26(19).

PMID: 34641429 PMC: 8510467. DOI: 10.3390/molecules26195886.

References

Frijstein M, Lok C, Short D, Singh K, Fisher R, Hancock B . The results of treatment with high-dose chemotherapy and peripheral blood stem cell support for gestational trophoblastic neoplasia. Eur J Cancer. 2019; 109:162-171. DOI: 10.1016/j.ejca.2018.12.033. View

Durocher D, Jackson S . DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?. Curr Opin Cell Biol. 2001; 13(2):225-31. DOI: 10.1016/s0955-0674(00)00201-5. View

Chen Y, Chen Y, Pan B, Chang M, Huang B . Functional study of Cordyceps sinensis and cordycepin in male reproduction: A review. J Food Drug Anal. 2017; 25(1):197-205. PMC: 9333433. DOI: 10.1016/j.jfda.2016.10.020. View

Panta G, Kaur S, Cavin L, Cortes M, Mercurio F, Lothstein L . ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol. 2004; 24(5):1823-35. PMC: 350545. DOI: 10.1128/MCB.24.5.1823-1835.2004. View

Lien W, Chen T, Sheu S, Lin T, Kang F, Yu C . 7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells. J Cell Biochem. 2017; 119(6):4729-4741. DOI: 10.1002/jcb.26652. View

Tsai Y, Lin L, Tsai T . Pharmacokinetics of adenosine and cordycepin, a bioactive constituent of Cordyceps sinensis in rat. J Agric Food Chem. 2010; 58(8):4638-43. DOI: 10.1021/jf100269g. View

Lee H, Kim S, Kim G, Moon S, Kim W, Jeong Y . Involvement of autophagy in cordycepin-induced apoptosis in human prostate carcinoma LNCaP cells. Environ Toxicol Pharmacol. 2014; 38(1):239-50. DOI: 10.1016/j.etap.2014.06.003. View

Ishikawa F, Ushida K, Mori K, Shibanuma M . Loss of anchorage primarily induces non-apoptotic cell death in a human mammary epithelial cell line under atypical focal adhesion kinase signaling. Cell Death Dis. 2015; 6:e1619. PMC: 4669778. DOI: 10.1038/cddis.2014.583. View

Li Y, Li R, Zhu S, Zhou R, Wang L, Du J . Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells. Oncol Lett. 2015; 9(6):2541-2547. PMC: 4473511. DOI: 10.3892/ol.2015.3066. View

10.

Ahn Y, Park S, Lee S, Shin S, Choi D . Cordycepin: selective growth inhibitor derived from liquid culture of Cordyceps militaris against Clostridium spp. J Agric Food Chem. 2000; 48(7):2744-8. DOI: 10.1021/jf990862n. View

11.

Park J, Jung C, Seo M, Otto N, Grunwald D, Kim K . The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy. 2016; 12(3):547-64. PMC: 4835982. DOI: 10.1080/15548627.2016.1140293. View

12.

Hinchcliffe E, Sluder G . "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. Genes Dev. 2001; 15(10):1167-81. DOI: 10.1101/gad.894001. View

13.

Liao Y, Ling J, Zhang G, Liu F, Tao S, Han Z . Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells. Cell Cycle. 2015; 14(5):761-71. PMC: 4615139. DOI: 10.1080/15384101.2014.1000097. View

14.

Bae H, Guan J . Suppression of autophagy by FIP200 deletion impairs DNA damage repair and increases cell death upon treatments with anticancer agents. Mol Cancer Res. 2011; 9(9):1232-41. PMC: 3175275. DOI: 10.1158/1541-7786.MCR-11-0098. View

15.

Lin Y, Shih H, Shang Z, Matsunaga S, Chen B . DNA-PKcs is required to maintain stability of Chk1 and Claspin for optimal replication stress response. Nucleic Acids Res. 2014; 42(7):4463-73. PMC: 3985680. DOI: 10.1093/nar/gku116. View

16.

Lee J, Adrower C, Qin C, Fischer P, de Moor C, Gershkovich P . Development of Cordycepin Formulations for Preclinical and Clinical Studies. AAPS PharmSciTech. 2017; 18(8):3219-3226. DOI: 10.1208/s12249-017-0795-0. View

17.

Wang C, Huang E, Huang S, Chung B . DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress. Oncogene. 2014; 34(10):1263-9. DOI: 10.1038/onc.2014.74. View

18.

Pan B, Wang Y, Lai M, Mu Y, Huang B . Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38 MAPKs and PI3K/AKT signaling pathways. Sci Rep. 2015; 5:13372. PMC: 4548195. DOI: 10.1038/srep13372. View

19.

Zeng Y, Lian S, Li D, Lin X, Chen B, Wei H . Anti-hepatocarcinoma effect of cordycepin against NDEA-induced hepatocellular carcinomas via the PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB pathway in mice. Biomed Pharmacother. 2017; 95:1868-1875. DOI: 10.1016/j.biopha.2017.09.069. View

20.

Li Y, Li K, Mao L, Han X, Zhang K, Zhao C . Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc. PeerJ. 2016; 4:e1992. PMC: 4867702. DOI: 10.7717/peerj.1992. View