bisdemethoxycurcumin and Neoplasm-Metastasis

Bisdemethoxycurcumin (BDMC) exhibits biological activities including anticancer and anti-metastasis in human cancer cell lines, but there is no available information to show whether BDMC suppresses cell migration and invasion of human cervical cancer cells.. Wound-healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of BDMC on HeLa cells in vitro.. BDMC reduced the total viable cell number in a dose-dependent manner. The wound-healing assay show BDMC suppressed the movement of HeLa cells. Furthermore, the trans-well chamber assays showed that BDMC suppressed the cell migration and invasion. Gelatin zymograph assay showed that BDMC did not inhibit matrix metalloproteinase-2 (MMP-2) and -9 activities in vitro. However, western blotting assay showed that BDMC significantly reduced protein levels of growth factor receptor-bound protein 2 (GRB2), Ras homolog gene family, member A (Rho A), urokinase-type plasminogen activator (uPA), RAS, MMP-2, and N-cadherin but increased those of phosphor-extracellular-signal related kinase (p-ERK1/2), E-cadherin and nuclear factor-ĸB (NF-ĸB) in HeLa cells. Confocal laser microscopy assay was used to further confirm BDMC increased NF-ĸB when compared to controls.. BDMC may have potential as a novel anti-metastasis agent for the treatment of human cervical cancer.

Topics: Blotting, Western; Curcumin; Diarylheptanoids; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Female; HeLa Cells; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Microscopy, Confocal; Neoplasm Invasiveness; Neoplasm Metastasis; NF-kappa B; Uterine Cervical Neoplasms

Aldo-keto reductase 1B10 (AKR1B10) is overexpressed in several extraintestinal cancers, particularly in non-small-cell lung cancer, where AKR1B10 is a potential diagnostic marker and therapeutic target. Selective AKR1B10 inhibitors are required because compounds should not inhibit the highly related aldose reductase that is involved in monosaccharide and prostaglandin metabolism. Currently, 7-hydroxy-2-(4-methoxyphenylimino)-2H-chromene-3-carboxylic acid benzylamide (HMPC) is known to be the most potent competitive inhibitor of AKR1B10, but it is nonselective. In this study, derivatives of HMPC were synthesized by removing the 4-methoxyphenylimino moiety and replacing the benzylamide with phenylpropylamide. Among them, 4c and 4e showed higher AKR1B10 inhibitory potency (IC

Topics: A549 Cells; Aldo-Keto Reductases; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Enzyme Inhibitors; Humans; Lung Neoplasms; Mutation; Neoplasm Metastasis