Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human
Kátia da Conceição Machado1, Lívia Queiroz de Sousa1, Daisy Jereissati Barbosa Lima2
1Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil.
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.
Insights
Marinobufagin, a toad secretion molecule, shows potent antiproliferative effects against human leukemia cells while sparing normal cells. This natural compound offers a promising avenue for cancer research and drug development.
Area of Science:
- Natural Products Chemistry
- Pharmacology
- Toxicology
Background:
- Skin toad secretions contain bioactive molecules for defense.
- Marinobufagin is a potentially therapeutic compound found in toad venom.
Purpose of the Study:
- To evaluate the antiproliferative activity of marinobufagin on tumor and normal cell lines.
- To investigate the mechanism of action on HL-60 leukemia cells.
- To assess the toxic effects of marinobufagin on Allium cepa meristematic cells.
Main Methods:
- Colorimetric assays for cytotoxicity.
- Morphological and flow cytometry analysis of HL-60 cells.
- Exposure of Allium cepa roots to marinobufagin for 72 hours.
Main Results:
- Marinobufagin exhibited significant antiproliferative action against human tumor lines (IC50: 0.15–7.35 μM), with notable efficacy against HL-60 leukemia cells.
- Normal human cells (PBMC, erythrocytes) and murine lines showed reduced sensitivity or no effect.
- Marinobufagin induced apoptosis, cell cycle arrest, and chromosomal abnormalities in HL-60 cells and Allium cepa root meristematic cells.
Conclusions:
- Marinobufagin demonstrates selective antiproliferative activity against human leukemia cells.
- The compound induces apoptosis and genotoxicity in cancer cells and plant models.
- Targeted natural molecules like marinobufagin represent a promising strategy in cancer therapy research.
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