title: Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling.
abstract: Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an IC50 value of 12.0 μg/mL, without affecting human normal liver cells, WRL-68 (IC50>50 μg/mL) causing G0/G1 cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of NF-κB that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC.
authors.affiliation: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia E-mail : reenaa.joys@gmail.com.
authors.forename: A Reenaa Joys
authors.initials: AR
authors.lastname: Andas
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.forename: Heshu Sulaiman
authors.initials: HS
authors.lastname: Rahman
authors.forename: Mohd Aspollah
authors.initials: MA
authors.lastname: Sukari
authors.forename: Siddig Ibrahim
authors.initials: SI
authors.lastname: Abdelwahab
authors.forename: Nozlena Abdul
authors.initials: NA
authors.lastname: Samad
authors.forename: Theebaa
authors.initials: T
authors.lastname: Anasamy
authors.forename: Ismail Adam
authors.initials: IA
authors.lastname: Arbab
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D054700:Clausena; D045304:Cytochromes c / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D016328:NF-kappa B; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C581591:dentatin; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9