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Involvement of MAPK, Bcl‐2 family, cytochrome c , and caspases in induction of apoptosis by 1,6‐ O,O ‐diacetylbritannilactone in human leukemia cells
Author(s) -
Pan MinHsiung,
Chiou YiSiou,
Cheng AnChin,
Bai Naisheng,
Lo ChihYu,
Tan Di,
Ho ChiTang
Publication year - 2007
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200600148
Subject(s) - apoptosis , cytochrome c , mapk/erk pathway , microbiology and biotechnology , kinase , caspase , reactive oxygen species , chemistry , mitochondrion , cytosol , phosphorylation , signal transduction , protein kinase a , bcl 2 family , biology , programmed cell death , biochemistry , enzyme
1,6‐ O,O ‐diacetylbritannilactone (OODBL) isolated from Inula britannica , exhibits potent antitumor activity against several human cancer cell lines. However, the molecular mechanism of OODBL in the induction of anticancer activity is still unclear. In the present study, we demonstrated that OODBL induced the occurrence of apoptosis in human leukemic (HL‐60) cells and cell arrest at the S phase. On the other hand, activation of caspase‐8, ‐9, and ‐3, phosphorylation of Bcl‐2 and Bid, and increased release of cytochrome c from mitochondria into cytosolic fraction were detected in OODBL‐treated HL‐60 cells. We further demonstrated that production of reactive oxygen species (ROS), activation of mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase (JNK) signaling pathways may play an important role in OODBL‐induced apoptosis. The results from the present study highlight the molecular mechanisms underlying OODBL‐induced anticancer activity.