Induction of apoptosis by pterocarpans from Platymiscium floribundum in HL-60 human leukemia cells.

Abstract

(+)-2,3,9-Trimethoxy-pterocarpan (1) (+)-3,9-dimethoxy-pterocarpan [(+)-homopterocarpin] (2), (+)-3-hydroxy-9-methoxy-pterocarpan [(+)-medicarpin] (3) and (+)-3,4-dihydroxy-9-methoxy-pterocarpan [(+)-vesticarpan] (4) are cytotoxic pterocarpans isolated from the native Brazilian plant Platymiscium floribundum. The purpose of the present study was to examine whether induction of apoptosis and/or inhibition of DNA synthesis is involved in the cytotoxicity of these pterocarpans in human leukemia cells. The effect on cell viability determined using the trypan exclusion assay revealed that all compounds tested reduced the number of viable cells, while only in the presence of 3 and 4, there was an increase of nonviable cells. The analysis of membrane integrity and morphological modifications by flow cytometry in the presence of these two compounds indicated that treated cells undergo necrosis, while 1 and 2 trigger apoptosis. DNA synthesis seemed to be affected since BrdU incorporation was inhibited in a dose-dependent manner in the presence of all tested compounds. Pterocarpan treatment also induced an increase in the amount of subdiploid DNA, indicating internucleosomal DNA breakdown, mitochondrial depolarization and caspase-3 activation, which indicate apoptosis induction.

• Authors: Gardenia C G Militão, Ivana N F Dantas, Cláudia Pessoa, Maria José C Falcão, Edilberto R Silveira, Mary Anne S Lima, Rui Curi, Thaís Lima, Manoel O Moraes, Letícia V Costa-Lotufo
• Journal: Life sciences (Life Sci) Vol. 78 Issue 20 Pg. 2409-17 (Apr 11 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16316665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Caspase Inhibitors
• DNA, Neoplasm
• Nucleosomes
• Pterocarpans
• CASP3 protein, human
• Caspase 3
• Trypan Blue

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Brazil
• Caspase 3
• Caspase Inhibitors
• Cell Membrane (drug effects, ultrastructure)
• DNA, Neoplasm (biosynthesis)
• Depression, Chemical
• Flow Cytometry
• HL-60 Cells
• Humans
• Membrane Potentials (drug effects)
• Mitochondria (drug effects)
• Nucleosomes (drug effects, ultrastructure)
• Plants, Medicinal (chemistry)
• Pterocarpans (pharmacology)
• Trypan Blue
• Wood