4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene.
Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, and tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.
Ku
Bo Mi
BM
Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea.
Ryu
Hyung Won
HW
Lee
Yeon Kyung
YK
Ryu
Jinhyun
J
Jeong
Joo Yeon
JY
Choi
Jungil
J
Cho
Hee Jun
HJ
Park
Ki Hun
KH
Kang
Sang Soo
SS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000627:therapeutic use*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D014335:Tropomyosin / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
C554454:4'-acetoamido-4-hydroxychalcone; D000970:Antineoplastic Agents; D047188:Chalcones; C490775:TPM1 protein, human; D014335:Tropomyosin; D017868:Cyclic AMP-Dependent Protein Kinases