title: F16, a fraction from Eurycoma longifolia jack extract, induces apoptosis via a caspase-9-independent manner in MCF-7 cells.
abstract: F16 is a plant-derived pharmacologically active fraction extracted from Eurycoma longifolia Jack. Previously, we have reported that F16 inhibited the proliferation of MCF-7 human breast cancer cells by inducing apoptotic cell death while having some degree of cytoselectivity on a normal human breast cell line, MCF-10A. In this study, we attempted to further elucidate the mode of action of F16. We found that the intrinsic apoptotic pathway was invoked, with the reduction of Bcl-2 protein. Then, executioner caspase-7 was cleaved and activated in response to F16 treatment. Furthermore, apoptosis in the MCF- 7 cells was accompanied by the specific proteolytic cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Surprisingly, caspase-9 and p53 were unchanged with F16 treatment. We believe that the F16-induced apoptosis in MCF-7 cells occurs independently of caspase-9 and p53. Taken together, these results suggest that F16 from E. longifolia exerts anti-proliferative action and growth inhibition on MCF-7 cells through apoptosis induction and that it may have anticancer properties.
authors.affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, National University of Malaysia, 43600 UKM Bangi, Selangor, Malaysia. thiamtsu@yahoo.com
authors.forename: Thiam Tsui
authors.initials: TT
authors.lastname: Tee
authors.forename: Yew Hoong
authors.initials: YH
authors.lastname: Cheah
authors.forename: Lope Pihie Azimahtol
authors.initials: LP
authors.lastname: Hawariah
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D035701:Eurycoma / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D010936:Plant Extracts; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053179:Caspase 7; D053453:Caspase 9