The cytotoxicity of Scytosiphon lomentaria against HL-60 promyelocytic leukemia cells.
This study examined the cytotoxicity of Scytosiphon lomentaria, using various cancer cell lines. The ethyl acetate (EtOAc) fraction of this alga showed the cytotoxicity to leukemia cells, including HL-60. When HL-60 cells were treated with its EtOAc fraction, several apoptotic characteristics, such as DNA fragmentation, chromatin condensation, and an increase of the population of sub-G1 hypodiploid cells, were observed. Moreover, the EtOAc fraction decreased c-Myc expression in a dose-dependent manner. In order to understand the mechanism of apoptosis induction by S. lomentaria, we examined the changes of Bcl-2 and Bax protein expression levels. The EtOAc fraction reduced Bcl-2, an antiapoptotic protein, but increased Bax, a proapoptotic protein, in a dose-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the expression of the active form (19 kDa) of caspase-3 increased, and the increase of their activities was demonstrated by the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3, to 85 kDa. The results suggest that the inhibitory effect of S. lomentaria on the growth of HL-60 appears to arise from the induction of apoptosis by way of the down-regulation of Bcl-2 and the activation of caspase.
Kim
Sang-Cheol
SC
Department of Medicine, College of Medicine, Cheju National University, Ara 1-dong, Jeju 690-756, South Korea.
Park
Soo-Young
SY
Hyoun
Jae-Hee
JH
Cho
Heeyeong
H
Kang
Ji-Hoon
JH
Lee
Young-Ki
YK
Park
Doek-Bae
DB
Yoo
Eun-Sook
ES
Kang
Hee-Kyoung
HK
D000085:Acetates / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D056890:Eukaryota / Q000378:metabolism*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013997:Time Factors; D051028:bcl-2-Associated X Protein
D000085:Acetates; C494826:BAX protein, human; D002843:Chromatin; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; C007650:ethyl acetate; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases