title: Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation.
abstract: The present study is on the growth inhibitory effect of Withania somnifera methanolic leaf extract and its active component, withanolide on HL-60 promyelocytic leukemia cells. The decrease in survival rate of HL-60 cells was noted to be associated with a time dependent decrease in the Bcl-2/Bax ratio, leading to up regulation of Bax. Both the crude leaf extract and the active component activated the apoptotic cascade through the cytochrome c release from mitochondria. The activation of caspase 9, caspase 8 and caspase 3 revealed that caspase was a key mediator in the apoptotic pathway. DNA fragmentation analysis revealed typical ladders as early as 12h indicative of caspase 3 role in the apoptotic pathway. Flow cytometry data demonstrated an increase of sub-G1 peak upon treatment by 51% at 24h, suggesting the induction of apoptotic cell death in HL-60 cells.
authors.affiliation: Centre For Biotechnology, Anna University, Chennai 600025, Tamil Nadu, India.
authors.forename: V
authors.initials: V
authors.lastname: Senthil
authors.forename: S
authors.initials: S
authors.lastname: Ramadevi
authors.forename: V
authors.initials: V
authors.lastname: Venkatakrishnan
authors.forename: P
authors.initials: P
authors.lastname: Giridharan
authors.forename: B S
authors.initials: BS
authors.lastname: Lakshmi
authors.forename: R A
authors.initials: RA
authors.lastname: Vishwakarma
authors.forename: A
authors.initials: A
authors.lastname: Balakrishnan
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D000432:Methanol / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D032341:Withania / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C519793:5alpha-ethoxy-1-oxo-6beta,14alpha,17beta,20-tetrahydroxy-20S,22R-witha-2,24-dienolide; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020112:Rhodamine 123; D045304:Cytochromes c; D053148:Caspase 3; D000432:Methanol; D004875:Ergosterol