title: Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells.
abstract: Apigenin is one of the plant-originated flavones with anticancer activities. In this study, apigenin was assessed for its in vitro effects on a human colon carcinoma line (HCT‑116 cells) in terms of anti-proliferation, cell cycle progression arrest, apoptosis and intracellular reactive oxygen species (ROS) generation, and then outlined its possible apoptotic mechanism for the cells. Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase, and decreased mitochondrial membrane potential of the treated cells. Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells. Apigenin shows apoptosis induction towards the cells, resulting in enhanced portion of apoptotic cells. A mechanism involved ROS generation and endoplasmic reticulum stress was outlined for the apigenin-mediated apoptosis via both intrinsic mitochondrial and extrinsic pathways, based on the assayed mRNA and protein expression levels in the cells. With this mechanism, apigenin resulted in the HCT-116 cells with enhanced intracellular ROS generation and Ca2+ release together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.
authors.affiliation: Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
authors.forename: Xin-Huai
authors.initials: XH
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D045325:HCT116 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D051742:Transcription Factor CHOP / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C497249:DDIT3 protein, human; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D051742:Transcription Factor CHOP; D047310:Apigenin; D020782:Matrix Metalloproteinases; D002118:Calcium