Beta-lapachone, a quinone isolated from Tabebuia avellanedae, induces apoptosis in HepG2 hepatoma cell line through induction of Bax and activation of caspase.
The DNA topoisomerase inhibitor beta-lapachone is a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) in South America. It has been reported to possess a wide range of pharmacological properties, and is a promising cancer chemopreventive agent. In this study, the effects of beta-lapachone on the growth of the human hepatoma cell line HepG2 were investigated. The results showed that beta-lapachone inhibits the viability of HepG2 by inducing apoptosis, as evidenced by the formation of apoptotic bodies and DNA fragmentation. Reverse transcription-polymerase chain reaction and immunoblotting results indicated that treatments of cells with beta-lapachone resulted in down-regulation of anti-apoptotic Bcl-2 and Bcl-X(L) and up-regulation of pro-apoptotic Bax expression. beta-Lapachone-induced apoptosis was associated with a proteolytic activation of caspase-3 and -9 and degradation of poly(ADP-ribose) polymerase protein. However, beta-lapachone treatment did not affect the inhibitor of apoptosis proteins family and the Fas/FasL system. Taken together, our study indicated that beta-lapachone may have potential as a chemopreventive agent for liver cancer.
Woo
Hyun Joo
HJ
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea.
Park
Kun-Young
KY
Rhu
Chung-Ho
CH
Lee
Won Ho
WH
Choi
Byung Tae
BT
Kim
Gi Young
GY
Park
Yeong-Min
YM
Choi
Yung Hyun
YH
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis; D008113:Liver Neoplasms; D008562:Membrane Glycoproteins / Q000032:analysis; D009285:Naphthoquinones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029663:Tabebuia / Q000737:chemistry*; D048069:Tumor Necrosis Factors / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000235:genetics; D019014:fas Receptor / Q000032:analysis
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D048069:Tumor Necrosis Factors; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C014638:beta-lapachone; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases