Anti-leukemic effects of the V-ATPase inhibitor Archazolid A

Zhang, Siwei; Schneider, Lina S.; Vick, Binje; Grunert, M; Jeremias, Irmela; Menche, Dirk; Müller, Rolf; Vollmar, Angelika M.; Liebl, Johanna

doi:10.18632/oncotarget.6180

Cited by 29 publications

(22 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Archazolid, a V-ATPase inhibitor, is highly effective against various cancer cell lines [ 158 ]. Recent research showed that Archazolid induced cell death by disturbing TFR recycling and impairing iron supply of cancer cells [ 159 , 160 ].…”

Section: Therapeutic Opportunities For Cancer Based On Altered Iromentioning

confidence: 99%

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

Zhou

Zhao

Zhang

et al. 2018

IJMS

View full text Add to dashboard Cite

Iron is an essential element for the growth and proliferation of cells. Cellular iron uptake, storage, utilization and export are tightly regulated to maintain iron homeostasis. However, cellular iron metabolism pathways are disturbed in most cancer cells. To maintain rapid growth and proliferation, cancer cells acquire large amounts of iron by altering expression of iron metabolism- related proteins. In this paper, normal cellular iron metabolism and the alterations of iron metabolic pathways in cancer cells were summarized. Therapeutic strategies based on targeting the altered iron metabolism were also discussed and disrupting redox homeostasis by intracellular high levels of iron provides new insight for cancer therapy. Altered iron metabolism constitutes a promising therapeutic target for cancer therapy.

show abstract

Section: Therapeutic Opportunities For Cancer Based On Altered Iromentioning

confidence: 99%

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

Zhou

Zhao

Zhang

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Archazolid has been intensively investigated as anti-tumoral agent that induced apoptosis of cancer cells and reduced migration of invasive tumor cells in vitro, and decreased metastatic dissemination of breast tumors in vivo [18][19][20]. In various highly invasive tumor cell lines and leukemic cells, archazolid led to apoptosis due to activation of the hypoxia-inducible factor-1α (HIF1α) [18,21], and to anoikis induction [22]. Thus, archazolid represents a promising candidate for direct targeting of tumor cells via V-ATPase inhibition.…”

Section: Introductionmentioning

confidence: 99%

Selective upregulation of TNFα expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase

Thomas

Rao

Gerstmeier

et al. 2017

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…ing V-ATPase activity using either pharmacological inhibitors or genetic approaches significantly reduces the invasiveness and migratory capacity of numerous cancer cell types (5,18,(21)(22)(23)(24)(25)(26)(27)(28). Specifically, plasma membrane V-ATPases appear to play a central role in cancer cell invasiveness (6).…”

mentioning

confidence: 99%

Isoform-specific gene disruptions reveal a role for the V-ATPase subunit a4 isoform in the invasiveness of 4T1-12B breast cancer cells

McGuire

Collins

Sun‐Wada

et al. 2019

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Alex TokerThe vacuolar H ؉ -ATPase (V-ATPase) is an ATP-driven proton pump present in various intracellular membranes and at the plasma membrane of specialized cell types. Previous work has reported that plasma membrane V-ATPases are key players in breast cancer cell invasiveness. The two subunit a-isoforms known to target the V-ATPase to the plasma membrane are a3 and a4, and expression of a3 has been shown to correlate with plasma membrane localization of the V-ATPase in various invasive human breast cancer cell lines. Here we analyzed the role of subunit a-isoforms in the invasive mouse breast cancer cell line, 4T1-12B. Quantitation of mRNA levels for each isoform by quantitative RT-PCR revealed that a4 is the dominant isoform expressed in these cells. Using a CRISPR/Cas9-based approach to disrupt the genes encoding each of the four V-ATPase subunit a-isoforms, we found that ablation of only the a4-encoding gene significantly inhibits invasion and migration of 4T1-12B cells. Additionally, cells with disrupted a4 exhibited reduced V-ATPase expression at the leading edge, suggesting that the a4 isoform is primarily responsible for targeting the V-ATPase to the plasma membrane in 4T1-12B cells. These findings suggest that different subunit a-isoforms may direct V-ATPases to the plasma membrane of different invasive breast cancer cell lines. They further suggest that expression of V-ATPases at the cell surface is the primary factor that promotes an invasive cancer cell phenotype. 3 The abbreviations used are: V-ATPase, vacuolar protein-translocating adenosine triphosphatase; ConA, concanamycin A; gRNA, guide RNA; ECAR, extracellular acidification rate; FBS, fetal bovine serum; PMSF, phenylmethylsulfonyl fluoride; DMEM, Dulbecco's modified Eagle's medium; DAPI, 4Ј,6-diamidino-2-phenylindole.

show abstract

Anti-leukemic effects of the V-ATPase inhibitor Archazolid A

Cited by 29 publications

References 74 publications

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

Selective upregulation of TNFα expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase

Isoform-specific gene disruptions reveal a role for the V-ATPase subunit a4 isoform in the invasiveness of 4T1-12B breast cancer cells

Contact Info

Product

Resources

About