Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines.
Acute lymphoblastic leukemia (ALL), especially T-acute lymphoblastic leukemia (T-ALL), is a common childhood malignant neoplastic disorder. Chemotherapy agents, particularly those that can induce apoptosis, are the major intervening strategy in the treatment of ALL. In this study, we investigated in T-ALL cell line, CCRF-CEM, the in vitro cytotoxic effect and the mechanism of action of baicalin, a compound extracted from Scutellaria baicalensis Georgi and S. rivularis Benth (Labiateae). Results demonstrated that baicalin displayed a remarkable cytotoxic effect in CCRF-CEM, with an IC(50) value of 10.6 microg/ml. It triggered apoptotic effect by fragmentizing cellular DNA and arrested the cell cycle at G(0)/G(1) phase. Baicalin (37.5 microg/ml) had not effected the expression of p53 and Fas protein. It was shown to decline the expression of Bcl-2 (22.0 pg/ml), which consequently caused the loss (52.7%) of transmembrane potential (Delta Psi m) in the mitochondria after 72 hours of treatment. Baicalin (37.5 microg/ml) also elevated the amount of cytosolic cytochrome c (19.2 microg/ml), which finally triggered the activation of caspase-3 (50.1 pmol/min). In conclusion, baicalin was found to induce apoptosis in T-ALL cell lines through multiple pathways. This finding encourages further investigation of baicalin in its role as a potential candidate for chemotherapeutic agents in T-ALL.
Shieh
Den-En
DE
Tajen Institute of Technology, Ping-Tung, Taiwan.
Cheng
Hua-Yew
HY
Yen
Ming-Hong
MH
Chiang
Lien-Chai
LC
Lin
Chun-Ching
CC
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D008564:Membrane Potentials; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C038044:baicalin; D045304:Cytochromes c; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases