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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 Publisher



Mirshamsi M1 ; Vazirizadeh A2 ; Omranipour R3 ; Fakhri A1 ; Aghvami M1 ; Naserzadeh P1 ; Zangeneh F1 ; Pourahmad J1
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Marine Toxinology, Persian Gulf Marine Biotechnology Research Center, Persian Gulf Biomedical Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
  3. 3. Department of Surgical Oncology, Cancer Institute, Emam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Hepatitis Monthly Published:2017


Abstract

Background: Globally, hepatocellular carcinoma (HCC) is the 3rd leading reason for mortality associated with cancer and the 6th most widespread malignant tumor. Objectives: This study aims to investigate selective toxicity of venom fractions of Pseudosynanceia melanostigma, commonly known as stonefish, on hepatocytes and mitochondria obtained from diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC). Methods: Different dilutions of extracted fractions from crude stonefish venom were treated on hepatocytes and mitochondria isolated from a rat model of hepatocellular carcinoma induced by diethylnitrosamine (DEN). In response to stonefish venom fractions, mitochondrial related parameters including generation of reactive oxygen species (ROS), mitochondrialmembranepotential (MMP) collapse, mitochondrial swelling, cytochrome c release, activation of caspase 3, and induction of apoptosis were investigated. Results: Our results demonstrate that for the first time, fraction 3 of Pseudosynanceia melanostigma treatment on cancerous mitochondria had a significant accumulation of reactive oxygen species (ROS). In addition, mitochondrial membrane potential (MMP) disruption, mitochondrial swelling, and cytochrome c release increased. Moreover, fraction 3 induced selective toxicity only in cancerous hepatocytes from the HCC but not those from healthy cells. Additional research also determined a significant increase in activation of caspase 3 and induction of apoptosis. Conclusions: In conclusion, this study provides evidence that fraction 3 of Pseudosynanceia melanostigmavenomselectively induces apoptosis in cancerous hepatocytes from HCC through a ROS-mediated mitochondrial pathway. © 2017, Hepatitis Monthly.