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Jellyfish venom is a rich source of bioactive proteins and peptides with various biological activities including antioxidant, antimicrobial and antitumor effects. However, the anti-proliferative activity of the crude extract of Rhopilema nomadica jellyfish venom has not been examined yet. The present study aimed at the investigation of the in vitro effect of R. nomadica venom on liver cancer cells (HepG2), breast cancer cells (MDA-MB231), human normal fibroblast (HFB4), and human normal lung cells (WI-38) proliferation by using MTT assay. The apoptotic cell death in HepG2 cells was investigated using Annexin V-FITC/PI double staining-based flow cytometry analysis, western blot analysis, and DNA fragmentation assays. R. nomadica venom displayed significant dose-dependent cytotoxicity on HepG2 cells after 48 h of treatment with IC 50 value of 50 μg/mL and higher toxicity (3:5-fold change) against MDA-MB231, HFB4, and WI-38 cells. R. nomadica venom showed a prominent increase of apoptosis as revealed by cell cycle arrest at G2/M phase, upregulation of p53, BAX, and caspase-3 proteins, and the down-regulation of anti-apoptotic Bcl-2 protein and DNA fragmentation. These findings suggest that R. nomadica venom induces apoptosis in hepatocellular carcinoma cells. To the best of the authors' knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest of R. nomadica jellyfish venom.

Competing Interests: The authors declare no conflict of interest.

Titel:	Nomad Jellyfish Rhopilema nomadica Venom Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Hepatocellular Carcinoma HepG2 Cells.
Autor/in / Beteiligte Person:	Tawfik, MM ; Eissa, N ; Althobaiti, F ; Fayad, E ; Abu Almaaty, AH
Link:	Full Text Finder (Volltext)
Zeitschrift:	Molecules (Basel, Switzerland), Jg. 26 (2021-08-26), Heft 17
Veröffentlichung:	Basel, Switzerland : MDPI, c1995-, 2021
Medientyp:	academicJournal
ISSN:	1420-3049 (electronic)
DOI:	10.3390/molecules26175185
Schlagwort:	Animals Apoptosis Regulatory Proteins metabolism Carcinoma, Hepatocellular metabolism Cell Line, Tumor Cell Proliferation drug effects Down-Regulation drug effects Hep G2 Cells Humans Liver Neoplasms metabolism Apoptosis drug effects Carcinoma, Hepatocellular drug therapy Cell Cycle Checkpoints drug effects Cell Death drug effects Cnidarian Venoms pharmacology Liver Neoplasms drug therapy Scyphozoa metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Molecules] 2021 Aug 26; Vol. 26 (17). <i>Date of Electronic Publication: </i>2021 Aug 26. MeSH Terms: Apoptosis / drug effects ; Carcinoma, Hepatocellular / drug therapy ; Cell Cycle Checkpoints / drug effects ; Cell Death / drug effects ; Cnidarian Venoms / pharmacology ; Liver Neoplasms / drug therapy ; Scyphozoa / *metabolism ; Animals ; Apoptosis Regulatory Proteins / metabolism ; Carcinoma, Hepatocellular / metabolism ; Cell Line, Tumor ; Cell Proliferation / drug effects ; Down-Regulation / drug effects ; Hep G2 Cells ; Humans ; Liver Neoplasms / metabolism References: J Cancer Epidemiol. 2014;2014:437971. (PMID: 25328522) ; Nature. 1970 Aug 15;227(5259):680-5. (PMID: 5432063) ; Bioorg Med Chem Lett. 2005 May 16;15(10):2659-64. (PMID: 15863337) ; Toxicol Pathol. 2007 Jun;35(4):495-516. (PMID: 17562483) ; Saudi J Biol Sci. 2021 Mar;28(3):1954-1961. (PMID: 33732081) ; Comp Biochem Physiol C Toxicol Pharmacol. 2016 Feb;180:31-9. (PMID: 26538054) ; Cell Tissue Res. 2000 Jul;301(1):5-17. (PMID: 10928277) ; Mar Environ Res. 2020 Dec;162:105161. (PMID: 33065521) ; Semin Cancer Biol. 2015 Apr;31:84-8. (PMID: 24859747) ; Anticancer Agents Med Chem. 2020;20(1):70-83. (PMID: 31696811) ; Anal Biochem. 1981 Apr;112(2):195-203. (PMID: 6266278) ; Toxicol Ind Health. 2012 Mar;28(2):186-92. (PMID: 21949089) ; Toxins (Basel). 2018 May 10;10(5):. (PMID: 29748501) ; J Egypt Natl Canc Inst. 2016 Dec;28(4):257-262. (PMID: 27378258) ; Mar Drugs. 2013 May 22;11(5):1728-62. (PMID: 23697954) ; Toxins (Basel). 2018 Mar 23;10(4):. (PMID: 29570625) ; Comp Biochem Physiol C Toxicol Pharmacol. 2009 Jul;150(1):85-90. (PMID: 19303056) ; Anal Biochem. 1976 May 7;72:248-54. (PMID: 942051) ; Toxicon. 2002 Apr;40(4):441-6. (PMID: 11738237) ; Asian Pac J Cancer Prev. 2012;13(10):4873-8. (PMID: 23244073) ; Curr Pharm Biotechnol. 2012 Jun;13(8):1426-38. (PMID: 22423614) ; J Biol Chem. 2014 Feb 21;289(8):4798-812. (PMID: 24403082) ; Sci Rep. 2018 Feb 12;8(1):2808. (PMID: 29434219) ; Toxicon. 2001 Sep;39(9):1297-307. (PMID: 11384717) ; Asian Pac J Cancer Prev. 2015;16(6):2129-44. (PMID: 25824729) ; Nature. 2000 Oct 12;407(6805):770-6. (PMID: 11048727) ; Cancer. 2005 Apr 15;103(8):1551-60. (PMID: 15742333) ; Wilderness Environ Med. 2018 Sep;29(3):343-356. (PMID: 29954662) ; N Engl J Med. 2019 Apr 11;380(15):1450-1462. (PMID: 30970190) ; Appl Microbiol Biotechnol. 2013 Jun;97(11):5069-77. (PMID: 23604560) ; J Anim Ecol. 2020 Mar;89(3):910-920. (PMID: 31782797) ; World J Gastroenterol. 2015 Apr 7;21(13):3826-42. (PMID: 25852267) ; Int J Mol Sci. 2018 Feb 02;19(2):. (PMID: 29393886) ; Semin Radiat Oncol. 2018 Oct;28(4):277-287. (PMID: 30309638) ; Cardiovasc Res. 2000 Feb;45(3):528-37. (PMID: 10728374) ; Asian Pac J Cancer Prev. ;18(1):277-286. (PMID: 28240847) ; CA Cancer J Clin. 2005 May-Jun;55(3):178-94. (PMID: 15890640) ; Lipids Health Dis. 2011 Dec 09;10:232. (PMID: 22151830) ; BMB Rep. 2014 Mar;47(3):167-72. (PMID: 24499665) ; PeerJ. 2017 Jan 19;5:e2895. (PMID: 28133573) ; World J Hepatol. 2017 Jul 28;9(21):907-920. (PMID: 28824742) ; Anal Biochem. 1994 May 1;218(2):314-9. (PMID: 8074286) ; Toxicol Lett. 2005 Feb 15;155(2):219-26. (PMID: 15603916) ; Toxicon. 1998 Aug;36(8):1075-85. (PMID: 9690776) ; Toxicol In Vitro. 2012 Aug;26(5):694-9. (PMID: 22445879) ; World J Hepatol. 2015 Jun 8;7(10):1412-20. (PMID: 26052386) ; Methods. 2008 Mar;44(3):200-4. (PMID: 18314050) ; Evid Based Complement Alternat Med. 2017;2017:2752716. (PMID: 28785288) ; Toxicon. 2007 Jul;50(1):53-64. (PMID: 17428515) ; Biomed Pharmacother. 2016 Dec;84:1986-1991. (PMID: 27876211) ; Toxicon. 2011 Apr;57(5):721-9. (PMID: 21333668) ; Ann Clin Microbiol Antimicrob. 2012 Jun 12;11:15. (PMID: 22691546) ; Toxicon. 2013 Sep;71:11-7. (PMID: 23688393) ; Biochim Biophys Acta. 2013 Dec;1833(12):3448-3459. (PMID: 23770045) ; J Venom Anim Toxins Incl Trop Dis. 2018 Apr 17;24:12. (PMID: 29692802) ; Comp Biochem Physiol A Mol Integr Physiol. 2008 Sep;151(1):144-9. (PMID: 18619552) Contributed Indexing: Keywords: HepG2; Rhopilema nomadica; apoptosis; cell cycle arrest Substance Nomenclature: 0 (Apoptosis Regulatory Proteins) ; 0 (Cnidarian Venoms) Entry Date(s): Date Created: 20210910 Date Completed: 20210923 Latest Revision: 20210923 Update Code: 20231215 PubMed Central ID: PMC8434601

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Nomad Jellyfish Rhopilema nomadica Venom Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Hepatocellular Carcinoma HepG2 Cells.