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Lee DH, Park T, Kim HW. Biol Pharm Bull. 2006 Apr;29(4):648-54
Induction of apoptosis by disturbing mitochondrial-membrane
potential and cleaving PARP in Jurkat T cells through treatment
with diacetoxyscirpenol and other acetoxyscirpenol mycotoxins.
Department of Life Sciences, University of Seoul, Korea.
Paecilomyces tenuipes is a famous Chinese medicinal
entomopathogenic fungus that grows within the larvae of
silkworms. 4beta-acetoxyscirpendiol (4-MAS), a cytotoxic
compound belonging to the scirpenol subfamily of trichothecene
mycotoxin, was isolated from Paecilomyces tenuipes. To further
elucidate the cytotoxic mechanism of 4-MAS, evidences of its
induction of apoptosis, together with the structurally related
acetoxyscirpenol moiety mycotoxins (ASMs) such as,
15-acetoxyscirpenol (15-MAS), 4,15-diacetoxyscirpenol
(4,15-DAS), and 3alpha-acetyldiacetoxyscirpenol (TAS), in the
human Jurkat T cell line were reported herein. In the MTT
reduction and time-course cytotoxicity assays for monitoring
cell viability, all the four ASMs that were tested exhibited
cytotoxicity; single acetoxylation at C-4 of the scirpenol
family resulted in relatively weak cytotoxicity, while
acetoxylation at C-15 resulted in strong cytotoxicity regardless
of the other acetoxylations at the C-3 and/or C-4 positions.
Phosphatidylserine externalization was induced by all the ASMs
that were treated at an early phase in a time-dependent manner,
showing a typical apoptotic phenomenon, not a necrotic one. The
ASMs also reduced the mitochondria's inner-membrane potential (deltaPsim)
through flow cytometry analysis after staining these with DiOC6,
a mitochondria-specific and voltage-dependent dye. Acetoxylation
of ASM at C-15 increased deltaPsim disruption, but that at C-3
reduced the deltaPsim. The ASMs that were tested also cleaved
113 kDa PARP to an 89-kDa fragment through Western blot assay,
suggesting the activation of caspase-3 and/or caspase-7 in the
Jurkat T cell. DNA fragmentation was also observed to have been
increased in a time-dependent manner by the ASMs that were
tested in Jurkat T cells, resulting in the DNA fragmentation
intensity order of 4,15-DAS>15-MAS>TAS>4-MAS. These data
indicate that the Jurkat T cells that were treated with ASMs
underwent typical cascades of apoptotic cell death.
PMID: 16595895 |
