The nematocysts venom of Chrysaora helvola Brandt leads to apoptosis-like cell death accompanied by uncoupling of oxidative phosphorylation

Toxicon. 2016 Feb:110:74-8. doi: 10.1016/j.toxicon.2015.12.011. Epub 2015 Dec 21.

Abstract

The present work investigated the effects of the nematocysts venom (NV) from the Chrysaora helvola Brandt (C. helvola) jellyfish on the human nasopharyngeal carcinoma cell line, CNE-2. The medium lethal concentration (LC50), quantified by MTT assays, was 1.7 ± 0.53 μg/mL (n = 5). An atypical apoptosis-like cell death was confirmed by LDH release assay and Annexin V-FITC/PI staining-based flow cytometry. Interestingly, activation of caspase-4 other than caspase-3, -8, -9 and -1 was observed. Moreover, the NV stimuli caused a time-dependent loss of mitochondrial membrane potential (ΔΨm) as was an intracellular ROS burst. These results indicated that there was uncoupling of oxidative phosphorylation (UOP). An examination of the intracellular pH value by a pH-sensitive fluorescent probe, BCECF, suggested that the UOP was due to the time-dependent increase in the intracellular pH. This is the first report that jellyfish venom can induce UOP.

Keywords: Atypical apoptosis; CNE-2; Caspase-4; Chrysaora helvola Brandt; Mitochondrial transmembrane potential; Nematocysts venom; Uncoupling of oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • China
  • Cnidarian Venoms / isolation & purification
  • Cnidarian Venoms / pharmacology*
  • Drug Discovery*
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lethal Dose 50
  • Membrane Potential, Mitochondrial / drug effects
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / metabolism
  • Nematocyst / chemistry
  • Nematocyst / growth & development
  • Oxidative Phosphorylation / drug effects*
  • Pacific Ocean
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Respiratory Mucosa / drug effects
  • Scyphozoa / chemistry*
  • Scyphozoa / growth & development
  • Uncoupling Agents / isolation & purification
  • Uncoupling Agents / pharmacology*

Substances

  • Antineoplastic Agents
  • Cnidarian Venoms
  • Reactive Oxygen Species
  • Uncoupling Agents
  • sea nettle toxin