Citation:
C. Ansah, H. Zhu, N. J. Goderham, The mechanism of ryptolepine-induced cell death. Journal of Pharmacology and Toxicology, 2008, Volume 3, Issue 4, pp291-301
Abstract:
The objective of the present study was to use morphological and biochemical
approaches to characterize the mode of CLP-induced cell death. Using a
differential staining technique, a Chinese Hamster fibroblast cell line (V79
cells) and a human lymphoblastoid cell line (MCL-5) showed morphology consistent
with apoptosis after treatment with CLP. In contrast, HepG2, a human hepatoma
cell line showed morphology that was more like necrosis after treatment with
CLP. Using annexin V staining for apoptotic cells, MCL-5 cells showed a three
fold increase in apoptosis within 6 h. Although we observed only a marginal
increase in BAX protein expression, cytochrome c was released into the cytosol
of CLP-treated MCL-5 cells. Furthermore, procaspase-3 was processed into the
active caspase-3 (17 kDa). Consistent with the caspase-3 activation, PARP was
cleaved to the typical 85 kDa fragment confirming apoptosis as the mode of cell
death in CLP-treated MCL-5 cells. However, there was no evidence of increased
BAX expression, cytochrome c release, caspase activation or PARP cleavage in
CLP-treated HepG2 cells. This observation together with the morphology of CLP-
treated HepG2 cells indicates that in contrast to MCL-5 cells, the CLP-mediated
demise of HepG2 cells is not apoptotic.