title: The growth suppressing effects of girinimbine on HepG2 involve induction of apoptosis and cell cycle arrest.
abstract: Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) peak (hypodiploid) and caused G(0)/G(1)-phase arrest. Together, these results demonstrated for the first time that girinimbine could effectively induce programmed cell death in HepG2 cells and suggests the importance of conducting further investigations in preclinical human hepatocellular carcinoma models, especially on in vivo efficacy, to promote girinimbine for use as an anticancer agent against hepatocellular carcinoma.
authors.affiliation: UPM-Makna Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. suvithasyam@aim.com
authors.forename: Suvitha
authors.initials: S
authors.lastname: Syam
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.forename: Mohd Aspollah
authors.initials: MA
authors.lastname: Sukari
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.forename: Siddig Ibrahim
authors.initials: SI
authors.lastname: Abdelwahab
authors.forename: Tang Sook
authors.initials: TS
authors.lastname: Wah
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D057075:Enzyme Assays; D006131:Growth Inhibitors / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D016192:Resting Phase, Cell Cycle
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D017077:Culture Media, Conditioned; D006131:Growth Inhibitors; C034052:girinimbine; D007770:L-Lactate Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3