Butein inhibits the proliferation of breast cancer cells through generation             of reactive oxygen species and modulation of ERK and p38 activities.
Butein (3,4,2',4'-tetrahydroxychalcone) is a polyphenol derived from various             natural plants and is capable of inducing several types of death in cancer cells.             However, the molecular mechanisms underlying butein-induced breast cancer cell             apoptosis remain unknown. The present study aimed to prove that butein inhibits             the proliferation of MDA-MB‑231 human breast cancer cells in a dose- and time-dependent             manner. Butein markedly induced the generation of reactive oxygen species (ROS),             decreased the phosphorylation of extracellular signal-regulated kinase (ERK),             increased p38 activity, diminished Bcl-2 expression, induced caspase 3 cleavage             and was associated with poly(ADP-ribose) polymerase (PARP) cleavage. Our findings             also indicate that ROS may play an important role in butein-induced apoptosis,             as pre-treatment with the antioxidant, N-acetyl cysteine (NAC), prevented butein-induced             apoptosis. In conclusion, our results demonstrate that butein inhibits the proliferation             of breast cancer cells through the generation of ROS and the modulation of ERK             and p38 activities. We also demonstrate that these effects may be abrogaged by             pre-treatment with NAC. Our results suggest that butein may function as a potential             therapeutic agent for the treatment of breast cancer.
Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan, ROC.
Li-Heng
LH
Yang
Ying-Jui
YJ
Ho
Jing-Feng
JF
Lin
Chi-Wei
CW
Yeh
Shao-Hsuan
SH
Kao
Li-Sung
LS
Hsu
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000975:Antioxidants; D047188:Chalcones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C040918:butein; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D000111:Acetylcysteine