Abstract
Baicalein has been reported to induce growth-inhibitory activity in vitro in human cancer cells; however, the molecular mechanism of action is not completely understood. A pharmacological dose (10-100 microM) of baicalein exerted a cytotoxic effect on human hepatoma J5 cells resulting in G2/M arrest and apoptosis. In addition to cytotoxicity in J5 cells, several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9 and -3 occurred. Baicalein induced AIF and Endo G release from mitochondria indicating that baicalein stimulates apoptosis through the caspase-independent pathway, while undergoing apoptosis, there was a remarkable accumulation of G2/M cells. Also, the ratio of Bax/Bcl-2 was increased leading to changes in mitochondria membrane potential (DeltaPsim) and release of cytochrome c, whereas the baicalein-induced apoptosis was partially abrogated by pretreatment with the pan-caspase inhibitor z-VAD-fmk, the accumulation of G2/M cells remained. These results demonstrate that the cytotoxicity of baicalein in J5 cells is attributable to apoptosis mainly involving G2/M-arrest in an ER-dependent manner, via a mitochondria-dependent caspase pathway and as well as contributions of AIF and Endo G pathways.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Chloromethyl Ketones / pharmacology
-
Antineoplastic Agents, Phytogenic / pharmacology
-
Apoptosis / drug effects*
-
Apoptosis Inducing Factor / metabolism
-
Calcium / metabolism
-
Carcinoma, Hepatocellular / enzymology*
-
Carcinoma, Hepatocellular / pathology
-
Caspase 3 / metabolism*
-
Caspase Inhibitors
-
Cell Cycle / drug effects
-
Cell Line, Tumor
-
Cell Shape / drug effects
-
Cell Survival / drug effects
-
Cysteine Proteinase Inhibitors / pharmacology
-
Cytochromes c / metabolism
-
DNA Damage
-
Dose-Response Relationship, Drug
-
Endodeoxyribonucleases / metabolism
-
Enzyme Activation
-
Flavanones / pharmacology*
-
Humans
-
Liver Neoplasms / enzymology*
-
Liver Neoplasms / pathology
-
Membrane Potential, Mitochondrial / drug effects
-
Mitochondria / drug effects*
-
Mitochondria / enzymology
-
Mitochondria / pathology
-
Proto-Oncogene Proteins c-bcl-2 / metabolism
-
Reactive Oxygen Species / metabolism
-
Signal Transduction / drug effects*
-
Time Factors
-
bcl-2-Associated X Protein / metabolism
Substances
-
AIFM1 protein, human
-
Amino Acid Chloromethyl Ketones
-
Antineoplastic Agents, Phytogenic
-
Apoptosis Inducing Factor
-
BAX protein, human
-
Caspase Inhibitors
-
Cysteine Proteinase Inhibitors
-
Flavanones
-
Proto-Oncogene Proteins c-bcl-2
-
Reactive Oxygen Species
-
bcl-2-Associated X Protein
-
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
-
baicalein
-
Cytochromes c
-
Endodeoxyribonucleases
-
endonuclease G
-
CASP3 protein, human
-
Caspase 3
-
Calcium