Involvement of MAPK, Bcl-2 family, cytochrome c, and caspases in induction of apoptosis by 1,6-O,O-diacetylbritannilactone in human leukemia cells.
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.
Pan
Min-Hsiung
MH
Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan. mhpan@mail.nkmu.edu.tw
Chiou
Yi-Siou
YS
Cheng
An-Chin
AC
Bai
Naisheng
N
Lo
Chih-Yu
CY
Tan
Di
D
Ho
Chi-Tang
CT
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D038143:Inula / Q000737:chemistry*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D007783:Lactones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; C500400:O, O-diacetylbritannilactone; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases