Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells

Toxicol Lett. 2018 Mar 15:285:121-131. doi: 10.1016/j.toxlet.2017.12.018. Epub 2017 Dec 26.

Abstract

Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC50 values ranging from 0.15 (leukemia) to 7.35 (larynx) μM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC50: 10.88 μM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC50: 7.5 μM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer.

Keywords: Allium cepa; Anticancer action; Apoptosis; Chromosomal alterations; Murine lines.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Bufanolides / isolation & purification
  • Bufanolides / pharmacology*
  • Bufanolides / toxicity
  • Bufonidae / metabolism
  • Cell Cycle / drug effects*
  • Cell Survival / drug effects
  • Comet Assay
  • DNA Breaks*
  • Dose-Response Relationship, Drug
  • Erythrocytes / drug effects
  • HL-60 Cells
  • Healthy Volunteers
  • Hemolysis / drug effects
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Meristem / cytology
  • Meristem / drug effects
  • Meristem / genetics
  • Micronuclei, Chromosome-Defective / chemically induced
  • Onions / cytology
  • Onions / drug effects*
  • Onions / genetics
  • Skin / metabolism
  • Young Adult

Substances

  • Antineoplastic Agents
  • Bufanolides
  • marinobufagenin