title: Inhibitory effects of butein on cancer metastasis and bioenergetic modulation.
abstract: Tumor metastasis is the major obstacle for cancer treatment. Previous studies have shown that butein exhibits antiangiogenesis property and anticancer effects in different kinds of human cancer cells. However, the effects of butein on metastasis and energy metabolism of cancer cells are mostly unknown. This study showed that butein significantly inhibited invasion of cancer cells without acting in a cytotoxic fashion. It was further demonstrated that butien dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model. Additionally, butein concentration-dependently repressed the expression and activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). The study indicated that butein may repress MMP-9 and uPA proteolytic activities and subsequently inhibit cancer metastasis via Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress cancer metastasis by down-regulating ATP synthesis via both oxidative and glycolytic metabolism. The results suggest that butein is a potential antimetastatic agent worthy of further development for cancer treatment.
authors.affiliation: Departments of Orthopaedics, #Dermatology, and ⊥Anesthesiology, Mackay Memorial Hospital , Taipei, Taiwan.
authors.forename: Shih-Chia
authors.initials: SC
authors.lastname: Liu
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.forename: Ching-Hu
authors.initials: CH
authors.lastname: Chung
authors.forename: Po-Chuan
authors.initials: PC
authors.lastname: Wang
authors.forename: Nan-Lin
authors.initials: NL
authors.lastname: Wu
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Cheng
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Lai
authors.forename: Hui-Lung
authors.initials: HL
authors.lastname: Sun
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Peng
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D061965:Matrix Metalloproteinase Inhibitors; C040918:butein; D000255:Adenosine Triphosphate; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9
keywords: bioenergetics; butein; metastasis