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Sophoranone, extracted from a traditional Chinese medicine Shan Dou Gen, induces apoptosis in human leukemia U937 cells via formation of reactive oxygen species and opening of mitochondrial permeability transition pores
Author(s) -
Kajimoto Sachiko,
Takanashi Noriko,
Kajimoto Tetsuya,
Xu Man,
Cao Judong,
Masuda Yutaka,
Aiuchi Toshihiro,
Nakajo Shigeo,
Ida Yoshiteru,
Nakaya Kazuyasu
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10414
Subject(s) - apoptosis , cytochrome c , u937 cell , mitochondrial permeability transition pore , mitochondrion , genistein , reactive oxygen species , biology , mitochondrial apoptosis induced channel , leukemia , monocytic leukemia , biochemistry , microbiology and biotechnology , chemistry , programmed cell death , immunology , endocrinology
Screening of various natural products in a search for novel inducers of apoptosis in human leukemia cells led us to identify the strong apoptosis‐inducing activity in a fraction extracted with methanol from the roots of Sophora subprostrata Chun et T. Chen. We purified the compound that induced apoptosis in human leukemia cells and identified it as sophoranone. Sophoranone inhibited cell growth and induced apoptosis in various lines of cells from human solid tumors, with 50% inhibition of growth of human stomach cancer MKN7 cells at 1.2 ± 0.3 μM. The growth‐inhibitory and apoptosis‐inducing activities of sophoranone for leukemia U937 cells were very much stronger than those of other flavonoids, such as daidzein, genistein and quercetin. At the early stages of treatment of U937 cells with sophoranone, reactive oxygen species were formed, mitochondrial permeability pores were opened and cytochrome c was released from mitochondria. Cytochrome c was also released upon treatment of isolated mitochondria with sophoranone. Inhibitors of complexes III and IV, but not complexes I and II, of the mitochondrial respiratory chain prevented the release of cytochrome c from isolated mitochondria by sophoranone, as well as the induction of apoptosis in U937 cells in response to sophoranone. Our results indicate that sophoranone might be a unique apoptosis‐inducing anticancer agent that targets mitochondria. © 2002 Wiley‐Liss, Inc.