archazolid-b and Neoplasms

archazolid-b has been researched along with Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for archazolid-b and Neoplasms

Article	Year
V-ATPase inhibition by archazolid leads to lysosomal dysfunction resulting in impaired cathepsin B activation in vivo. International journal of cancer, 2014, May-15, Volume: 134, Issue:10 The myxobacterial agent archazolid inhibits the vacuolar proton pump V-ATPase. V-ATPases are ubiquitously expressed ATP-dependent proton pumps, which are known to regulate the pH in endomembrane systems and thus play a crucial role in endo- and exocytotic processes of the cell. As cancer cells depend on a highly active secretion of proteolytic proteins in order to invade tissue and form metastases, inhibition of V-ATPase is proposed to affect the secretion profile of cancer cells and thus potentially abrogate their metastatic properties. Archazolid is a novel V-ATPase inhibitor. Here, we show that the secretion pattern of archazolid treated cancer cells includes various prometastatic lysosomal proteins like cathepsin A, B, C, D and Z. In particular, archazolid induced the secretion of the proforms of cathepsin B and D. Archazolid treatment abrogates the cathepsin B maturation process leading to reduced intracellular mature cathepsin B protein abundance and finally decreased cathepsin B activity, by inhibiting mannose-6-phoshate receptor-dependent trafficking. Importantly, in vivo reduced cathepsin B protein as well as a decreased proteolytic cathepsin B activity was detected in tumor tissue of archazolid-treated mice. Our results show that inhibition of V-ATPase by archazolid reduces the activity of prometastatic proteases like cathepsin B in vitro and in vivo. Topics: Animals; Blotting, Western; Cathepsin B; Cell Line, Tumor; Enzyme Activation; Gene Expression Regulation, Neoplastic; Humans; Lysosomes; Macrolides; MCF-7 Cells; Mice; Mice, Inbred BALB C; Neoplasms; Neoplasms, Experimental; Protein Transport; Receptor, IGF Type 2; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Thiazoles; Tumor Burden; Vacuolar Proton-Translocating ATPases	2014
Synthesis and activity of the archazolid western hemisphere. Organic & biomolecular chemistry, 2011, Oct-26, Volume: 9, Issue:22 A convergent and scalable synthesis of the archazolid western hemisphere has been completed. The V-ATPase inhibitory activity of this compound along with a previously prepared eastern domain was then tested using a convenient Arabidopsis-based V-ATPase assay. Topics: Animals; Antineoplastic Agents; Arabidopsis; Biological Assay; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Macrolides; Neoplasms; Potoroidae; Thiazoles; Vacuolar Proton-Translocating ATPases; Vacuoles	2011

Article

Year

V-ATPase inhibition by archazolid leads to lysosomal dysfunction resulting in impaired cathepsin B activation in vivo.

International journal of cancer, 2014, May-15, Volume: 134, Issue:10

The myxobacterial agent archazolid inhibits the vacuolar proton pump V-ATPase. V-ATPases are ubiquitously expressed ATP-dependent proton pumps, which are known to regulate the pH in endomembrane systems and thus play a crucial role in endo- and exocytotic processes of the cell. As cancer cells depend on a highly active secretion of proteolytic proteins in order to invade tissue and form metastases, inhibition of V-ATPase is proposed to affect the secretion profile of cancer cells and thus potentially abrogate their metastatic properties. Archazolid is a novel V-ATPase inhibitor. Here, we show that the secretion pattern of archazolid treated cancer cells includes various prometastatic lysosomal proteins like cathepsin A, B, C, D and Z. In particular, archazolid induced the secretion of the proforms of cathepsin B and D. Archazolid treatment abrogates the cathepsin B maturation process leading to reduced intracellular mature cathepsin B protein abundance and finally decreased cathepsin B activity, by inhibiting mannose-6-phoshate receptor-dependent trafficking. Importantly, in vivo reduced cathepsin B protein as well as a decreased proteolytic cathepsin B activity was detected in tumor tissue of archazolid-treated mice. Our results show that inhibition of V-ATPase by archazolid reduces the activity of prometastatic proteases like cathepsin B in vitro and in vivo.

Topics: Animals; Blotting, Western; Cathepsin B; Cell Line, Tumor; Enzyme Activation; Gene Expression Regulation, Neoplastic; Humans; Lysosomes; Macrolides; MCF-7 Cells; Mice; Mice, Inbred BALB C; Neoplasms; Neoplasms, Experimental; Protein Transport; Receptor, IGF Type 2; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Thiazoles; Tumor Burden; Vacuolar Proton-Translocating ATPases

2014

Synthesis and activity of the archazolid western hemisphere.

Organic & biomolecular chemistry, 2011, Oct-26, Volume: 9, Issue:22

A convergent and scalable synthesis of the archazolid western hemisphere has been completed. The V-ATPase inhibitory activity of this compound along with a previously prepared eastern domain was then tested using a convenient Arabidopsis-based V-ATPase assay.

Topics: Animals; Antineoplastic Agents; Arabidopsis; Biological Assay; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Macrolides; Neoplasms; Potoroidae; Thiazoles; Vacuolar Proton-Translocating ATPases; Vacuoles

2011