Abrus abrin derived peptides induce apoptosis by targeting mitochondria in HeLa cells.
In our previous study, Abrus abrin derived peptide fraction (ABP) with molecular weight in range of 600-1500Da was shown to have potent antitumor activity in Dalton's lymphoma (DL) tumor bearing mice. The purpose of this study was to elucidate the mechanism of mitochondrial apoptosis induced by the peptide fraction. ABP was found to have selective antiproliferative activity (10ng-100ng/ml) on several tumor cell lines in vitro without having any cytotoxic effect on normal cell lines with a dose of 1000ng/ml. Analysis of the growth inhibitory mechanism in HeLa cells revealed DNA fragmentation with appearance of the sub G(0)/G(1) peak indicative of apoptosis. Further investigation results showed that the apoptotic machinery of HeLa induced by ABP was associated with the release of reactive oxygen species, a drop in mitochondrial transmembrane potential, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3. The peptide fraction was found to target mitochondria of HeLa cells as observed by confocal microscopy. This peptide fraction offers a source of mitochondria penetrating peptides which might have therapeutic induction of apoptosis in cancer cells.
Department of Biotechnology, Indian Institute of Technology, West Bengal, India.
Sujit K
SK
Bhutia
Sanjaya K
SK
Mallick
Swatilekha
S
Maiti
Debasish
D
Mishra
Tapas K
TK
Maiti
D000036:Abrin / Q000737:chemistry*; D029912:Abrus / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D010455:Peptides; D051028:bcl-2-Associated X Protein; D000036:Abrin; D053148:Caspase 3