Hepatitis Monthly

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Persian Gulf Stonefish (Pseudosynanceia melanostigma) Venom Fractions Selectively Induce Apoptosis on Cancerous Hepatocytes from Hepatocellular Carcinoma Through ROS-Mediated Mitochondrial Pathway

Mohammadreza Mirshamsi 1 , Amir Vazirizadeh 2 , Ramesh Omranipour 3 , Amir Fakhri 1 , Marjan Aghvami 1 , Parvaneh Naserzadeh 1 , Fatemeh Zangeneh 1 and Jalal Pourahmad 1 , *
Authors Information
1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Marine Toxinology, Persian Gulf Marine Biotechnology Research Center, Persian Gulf Biomedical Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
3 Department of Surgical Oncology, Cancer Institute, Emam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
Article information
  • Hepatitis Monthly: November 2017, 17 (11); e11842
  • Published Online: October 26, 2017
  • Article Type: Research Article
  • Received: April 18, 2017
  • Revised: August 30, 2017
  • Accepted: October 7, 2017
  • DOI: 10.5812/hepatmon.11842

To Cite: Mirshamsi M, Vazirizadeh A, Omranipour R, Fakhri A, Aghvami M, et al. Persian Gulf Stonefish (Pseudosynanceia melanostigma) Venom Fractions Selectively Induce Apoptosis on Cancerous Hepatocytes from Hepatocellular Carcinoma Through ROS-Mediated Mitochondrial Pathway, Hepat Mon. 2017 ; 17(11):e11842. doi: 10.5812/hepatmon.11842.

Copyright © 2017, Hepatitis Monthly. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5)-86[DOI][PubMed]
  • 2. Zhang Z, Zhang H, Peng T, Li D, Xu J. Melittin suppresses cathepsin S-induced invasion and angiogenesis via blocking of the VEGF-A/VEGFR-2/MEK1/ERK1/2 pathway in human hepatocellular carcinoma. Oncol Lett. 2016; 11(1): 610-8[DOI][PubMed]
  • 3. Zhang L, Cui L. A cytotoxin isolated from Agkistrodon acutus snake venom induces apoptosis via Fas pathway in A549 cells. Toxicol In Vitro. 2007; 21(6): 1095-103[DOI][PubMed]
  • 4. Gupta SD, Gomes A, Debnath A, Saha A, Gomes A. Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Chem Biol Interact. 2010; 183(2): 293-303[DOI][PubMed]
  • 5. Sivan G. Fish venom: pharmacological features and biological significance. Fish Fish. 2009; 10(2): 159-72[DOI]
  • 6. Carrijo LC, Andrich F, de Lima ME, Cordeiro MN, Richardson M, Figueiredo SG. Biological properties of the venom from the scorpionfish (Scorpaena plumieri) and purification of a gelatinolytic protease. Toxicon. 2005; 45(7): 843-50[DOI][PubMed]
  • 7. Gwee MC, Gopalakrishnakone P, Yuen R, Khoo HE, Low KS. A review of stonefish venoms and toxins. Pharmacol Ther. 1994; 64(3): 509-28[DOI][PubMed]
  • 8. Ueda A, Suzuki M, Honma T, Nagai H, Nagashima Y, Shiomi K. Purification, properties and cDNA cloning of neoverrucotoxin (neoVTX), a hemolytic lethal factor from the stonefish Synanceia verrucosa venom. Biochim Biophys Acta. 2006; 1760(11): 1713-22[DOI][PubMed]
  • 9. Yazawa K, Wang JW, Hao LY, Onoue Y, Kameyama M. Verrucotoxin, a stonefish venom, modulates calcium channel activity in guinea-pig ventricular myocytes. Br J Pharmacol. 2007; 151(8): 1198-203[DOI][PubMed]
  • 10. Church JE, Hodgson WC. Dose-dependent cardiovascular and neuromuscular effects of stonefish (Synanceja trachynis) venom. Toxicon. 2000; 38(3): 391-407[DOI][PubMed]
  • 11. Vazirizadeh A, Naderi-Manesh H, Bargahi A, Nabipour I, Mohebbi GH. Impacts of Persian Gulf blackfin stonefish crude venom on the haematological factors and serum enzymes levels of laboratory rat [In Persian]. Iran South Med J. 2014; 17(4): 723-32
  • 12. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-54[DOI][PubMed]
  • 13. Matsuzaki T, Murase N, Yagihashi A, Shinozuka H, Shimizu Y, Furuya T, et al. Liver transplantation for diethylnitrosamine-induced hepatocellular carcinoma in rats. Transplant Proc. 1992; 24(2): 748-51[PubMed]
  • 14. Pourahmad J, Eskandari MR, Nosrati M, Kobarfard F, Khajeamiri AR. Involvement of mitochondrial/lysosomal toxic cross-talk in ecstasy induced liver toxicity under hyperthermic condition. Eur J Pharmacol. 2010; 643(2-3): 162-9[DOI][PubMed]
  • 15. Barogi S, Baracca A, Parenti Castelli G, Bovina C, Formiggini G, Marchetti M, et al. Lack of major changes in ATPase activity in mitochondria from liver, heart, and skeletal muscle of rats upon ageing. Mech Ageing Dev. 1995; 84(2): 139-50[DOI][PubMed]
  • 16. Hosseini MJ, Shaki F, Ghazi-Khansari M, Pourahmad J. Toxicity of vanadium on isolated rat liver mitochondria: a new mechanistic approach. Metallomics. 2013; 5(2): 152-66[DOI][PubMed]
  • 17. Gao X, Zheng CY, Yang L, Tang XC, Zhang HY. Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide. Free Radic Biol Med. 2009; 46(11): 1454-62[DOI][PubMed]
  • 18. Rotem R, Heyfets A, Fingrut O, Blickstein D, Shaklai M, Flescher E. Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Res. 2005; 65(5): 1984-93[DOI][PubMed]
  • 19. Talari M, Seydi E, Salimi A, Mohsenifar Z, Kamalinejad M, Pourahmad J. Dracocephalum: novel anticancer plant acting on liver cancer cell mitochondria. Biomed Res Int. 2014; 2014: 892170[DOI][PubMed]
  • 20. Pourahmad J, Eskandari MR, Shakibaei R, Kamalinejad M. A search for hepatoprotective activity of aqueous extract of Rhus coriaria L. against oxidative stress cytotoxicity. Food Chem Toxicol. 2009; 48(3): 854-8[DOI][PubMed]
  • 21. Riccardi C, Nicoletti I. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc. 2006; 1(3): 1458-61[DOI][PubMed]
  • 22. Brenner C, Grimm S. The permeability transition pore complex in cancer cell death. Oncogene. 2006; 25(34): 4744-56[DOI][PubMed]
  • 23. Biasutto L, Dong LF, Zoratti M, Neuzil J. Mitochondrially targeted anti-cancer agents. Mitochondrion. 2010; 10(6): 670-81[DOI][PubMed]
  • 24. Mates JM, Sanchez-Jimenez FM. Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol. 2000; 32(2): 157-70[DOI][PubMed]
  • 25. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004; 7(2): 97-110[DOI][PubMed]
  • 26. Pelicano H, Feng L, Zhou Y, Carew JS, Hileman EO, Plunkett W, et al. Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. J Biol Chem. 2003; 278(39): 37832-9[DOI][PubMed]
  • 27. Kowaltowski AJ, Castilho RF, Vercesi AE. Mitochondrial permeability transition and oxidative stress. FEBS Lett. 2001; 495(1-2): 12-5[DOI][PubMed]
  • 28. Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010; 48(6): 749-62[DOI][PubMed]
  • 29. Kemparaju K, Girish KS. Snake venom hyaluronidase: a therapeutic target. Cell Biochem Funct. 2006; 24(1): 7-12[DOI][PubMed]
  • 30. Debnath A, Chatterjee U, Das M, Vedasiromoni JR, Gomes A. Venom of Indian monocellate cobra and Russell's viper show anticancer activity in experimental models. J Ethnopharmacol. 2007; 111(3): 681-4[DOI][PubMed]
  • 31. Karthikeyan R, Karthigayan S, Sri Balasubashini M, Somasundaram ST, Balasubramanian T. Inhibition of Hep2 and HeLa cell proliferation in vitro and EAC tumor growth in vivo by Lapemis curtus (Shaw 1802) venom. Toxicon. 2008; 51(1): 157-61[DOI][PubMed]
  • 32. Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia. 2002; 39(2): 162-73[DOI][PubMed]
  • 33. Aghvami M, Zarei MH, Mirshamsi MR, Pourahmad J. Selective toxicity of Persian Gulf Stonefish (Pseudosynanceia melanostigma) venom on human acute lymphocytic leukemia B-lymphocytes. Trend Peptide Protein Sci. 2017; 1(2): 56-60
  • 34. Soprani J. Identification of anti-tumoral effect of a polypeptide isolated from Scorpionfish Scorpaena plumieri venom and assessment of its potential use for tumor diagnosis. 2008;
  • 35. Sri Balasubashini M, Karthigayan S, Somasundaram ST, Balasubramanian T, Rukkumani R, Menon VP. FV peptide induces apoptosis in HEp 2 and HeLa cells: an insight into the mechanism of induction. J Carcinog. 2006; 5: 27[DOI][PubMed]
  • 36. Shinohara M, Nagasaka K, Nakagawa H, Edo K, Sakai H, Kato K, et al. A novel chemoattractant lectin, karatoxin, from the dorsal spines of the small scorpionfish Hypodytes rubripinnis. J Pharmacol Sci. 2010; 113(4): 414-7[DOI][PubMed]
  • 37. Ota E, Nagashima Y, Shiomi K, Sakurai T, Kojima C, Waalkes MP, et al. Caspase-independent apoptosis induced in rat liver cells by plancitoxin I, the major lethal factor from the crown-of-thorns starfish Acanthaster planci venom. Toxicon. 2006; 48(8): 1002-10[DOI][PubMed]
  • 38. Sri Balasubashini M, Karthigayan S, Somasundaram ST, Balasubramanian T, Viswanathan V, Raveendran P, et al. Fish venom (Pterios volitans) peptide reduces tumor burden and ameliorates oxidative stress in Ehrlich's ascites carcinoma xenografted mice. Bioorg Med Chem Lett. 2006; 16(24): 6219-25[DOI][PubMed]
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