Induction of apoptotic cell death by mycelium extracts of Phellinus linteus in human neuroblastoma cells.
Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the effects of mycelium extracts of P. linteus (MEPL) on the growth of human neuroblastoma SK-N-MC cells. Upon treatment with MEPL, a concentration-dependent inhibition of cell proliferation was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin and an increase in the sub-G1 population. The anti-proliferative and apoptotic effects of MEPL were associated with a marked induction of the Bax and cyclin-dependent kinase inhibitor p21. Western blotting and in vitro caspase-3 activity assay demonstrated that the processing/activation of caspases accompanies the generation of MEPL-mediating apoptotic cell death. In addition, the proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase and beta-catenin were observed. Taken together, the present results suggest that apoptotic signals evoked by MEPL in human neuroblastoma SK-N-MC cells may converge caspase-3 activation through an up-regulation of Bax rather than a down-regulation of Bcl-2.
Choi
Yung Hyun
YH
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea. choiyh@deu.ac.kr
Huh
Man Kyu
MK
Ryu
Chung-Ho
CH
Choi
Byung Tae
BT
Jeong
Young-Kee
YK
D000363:Agaricales / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D015151:Immunoblotting; D025282:Mycelium / Q000378:metabolism*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; D004396:Coloring Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D012313:RNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue