title: Dentatin Induces Apoptosis in Prostate Cancer Cells via Bcl-2, Bcl-xL, Survivin Downregulation, Caspase-9, -3/7 Activation, and NF-κB Inhibition.
abstract: This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules (Bcl-2, Bcl-xL, and Survivin), leading to disruption of mitochondrial membrane potential (MMP), cell membrane permeability, and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-9, -3/7 activities, and subsequent DNA fragmentation. In addition, we found that dentatin inhibited TNF-α-induced nuclear translocation of p65, suggesting dentatin as a potential NF-κB inhibitor. Thus, we suggest that dentatin may have therapeutic value in prostate cancer treatment worthy of further development.
authors.affiliation: Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Malaysia.
authors.forename: Ismail Adam
authors.initials: IA
authors.lastname: Arbab
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.forename: Foo Kit
authors.initials: FK
authors.lastname: Cheah
authors.forename: Won Fen
authors.initials: WF
authors.lastname: Wong
authors.forename: Mohd Aspollah
authors.initials: MA
authors.lastname: Sukari
authors.forename: Rasedee
authors.initials: R
authors.lastname: Abdullah
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.forename: Suvitha
authors.initials: S
authors.lastname: Syam
authors.forename: Aditya
authors.initials: A
authors.lastname: Arya
authors.forename: Manal
authors.initials: M
authors.lastname: Mohamed Elhassan Taha
authors.forename: Bushra
authors.initials: B
authors.lastname: Muharram
authors.forename: Mohd
authors.initials: M
authors.lastname: Rais Mustafa
authors.forename: Siddig
authors.initials: S
authors.lastname: Ibrahim Abdelwahab