Anti-hepatoma cells function of luteolin through inducing apoptosis and cell cycle arrest
- 28 November 2013
- journal article
- Published by Springer Science and Business Media LLC in Tumor Biology
- Vol. 35 (4), 3053-3060
- https://doi.org/10.1007/s13277-013-1396-5
Abstract
The aim of this study is to explore the apoptotic induction and cell cycle arrest function of luteolin on the liver cancer cells and the related mechanism. The liver cancer cell line SMMC-7721, BEL-7402, and normal liver cells HL-7702 were treated with different concentrations of luteolin. Cell proliferation ability was tested. Morphological changes of the apoptotic cells were observed under inverted fluorescence microscope after Hoechst33342 staining. We investigated the effect of luteolin on cell cycling and apoptosis with flow cytometry. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Caspases-3 and Bcl-2 family proteins expression were analyzed by real-time PCR. Cell proliferation of SMMC-7721 and BEL-7402 were inhibited by luteolin, and the inhibition was dose–time-dependent. Luteolin could arrest the cells at G1/S stage, reduce mitochondrial membrane potential, and induce higher apoptosis rate and the typical apoptotic morphological changes of the liver carcinoma cells. Q-RT-PCR results also showed that luteolin increased Bax and caspase-3 expression significantly and upregulated Bcl-2 expression in a dose-dependent manner in liver carcinoma cells. However, the normal liver cells HL-7702 was almost not affected by luteolin treatment. Luteolin can inhibit SMMC-7721 and BEL-7402 cell proliferation in a time- and dose-dependent manner. And the mechanism maybe through arresting cell cycle at phase G1/S, enhancing Bax level, reducing anti-apoptotic protein Bcl-2 level, resulting in activating caspase-3 enzyme and decrease of mitochondrial membrane potential, and finally leading to cell apoptosis.Keywords
This publication has 14 references indexed in Scilit:
- Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: Mitochondria mediated apoptotic signalling cascadesFood and Chemical Toxicology, 2013
- Tetrandrine Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer BGC-823 CellsPLOS ONE, 2013
- Luteolin Inhibits Inflammatory Responses via p38/MK2/TTP-mediated mRNA StabilityMolecules, 2013
- Protective Effect of Luteolin on an Oxidative-Stress Model Induced by Microinjection of Sodium Nitroprusside in MiceJournal of Pharmacological Sciences, 2013
- Epigenetics of hepatocellular carcinoma: Role of microRNAWorld Journal of Gastroenterology, 2013
- The effects of dexamethasone on the apoptosis and osteogenic differentiation of human periodontal ligament cellsJournal of Periodontal & Implant Science, 2013
- Luteolin Inhibits Human Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated AngiogenesisPLOS ONE, 2012
- Luteolin Induces Carcinoma Cell Apoptosis through Binding Hsp90 to Suppress Constitutive Activation of STAT3PLOS ONE, 2012
- Mitochondrial signaling in cell death via the Bcl-2 familyCancer Biology & Therapy, 2010
- A Critical Role of Luteolin-Induced Reactive Oxygen Species in Blockage of Tumor Necrosis Factor-Activated Nuclear Factor-κB Pathway and Sensitization of Apoptosis in Lung Cancer CellsMolecular Pharmacology, 2007