Heyneanol A induces apoptosis via cytochrome c release and caspase activation in human leukemic U937 cells.
Heyneanol A, a tetramer of resveratrol, is isolated from the roots of Vitis amurensis by cytotoxicity based fractionation. In this study, the mechanism of apoptosis by heyneanol A was evaluated in human leukemic U937 cells. Heyneanol A (IC(50) = 6.6 microM at 24 h) exhibited stronger cytotoxic effect than resveratrol (IC(50) = 100 microM at 24 h) by 15-fold on human leukemic U937 cells by XTT assay. Apoptotic bodies were observed in U937 cells treated with 6 microM of heyneanol A by TUNEL assay. Heyneanol A effectively increased the portion of sub-G(1) DNA content in a time- and concentration-dependent manner by flow cytometric analysis. Heyneanol A also induced cytochrome c release from mitochondria into the cytosol and subsequent caspase activation involving caspase 9 and 3 to cleave PARP. However, it did not affect the expressions of Bax and Bcl-2 by western blotting. It was confirmed that the activation of caspase 8, 9 and 3 and the cleavage of PARP by heyneanol A were completely blocked by adding Z-VAD-FMK, a caspase inhibitor. These findings suggest that heyneanol A has anti-tumor activity, which may be mediated by apoptosis caused by cytochrome c release and caspase activation in human leukemic U937 cells.
Lee
Eun-Ok
EO
Department of Oncology, Graduate School of East-West Medical Science, Kyung Hee University, 1 Seochunri, Kiheungeup, Yongin 449-701, South Korea. sungkim7@khu.ac.kr
Kwon
Byoung-Mog
BM
Song
Gyu-Yong
GY
Chae
Chan-Hee
CH
Kim
Hyung-Min
HM
Shim
In-Sop
IS
Ahn
Kyoo-Seok
KS
Kim
Sung-Hoon
SH
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D004789:Enzyme Activation; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D020298:U937 Cells; D027843:Vitis / Q000737:chemistry
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D013267:Stilbenes; C482862:heyneanol A; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D000077185:Resveratrol