Non-apoptotic concentrations of prodigiosin (H+/Cl− symporter) inhibit the acidification of lysosomes and induce cell cycle blockage in colon cancer cells

Castillo, Wilmar; Abal, Miguel; Robine, Sylvie; Pérez-Tomás, Ricardo

doi:10.1016/j.lfs.2005.04.059

Cited by 42 publications

(31 citation statements)

References 28 publications

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“…However, prodigiosininduced apoptosis via the death receptor signaling extrinsic pathway is also important, as it was reported not to involve p53 signaling 7 . In fact, as supported by our results, prodigiosins are known to cause apoptosis both dependently 8 and independently [8][9][10] of p53 tumor suppressor protein. The prodigiosins were cytotoxic toward HL60, U937 and K562 leukemia cell lines with varying IC 50 values.…”

Section: Discussionsupporting

confidence: 87%

Effects of prodigiosin family compounds fromPseudoalteromonassp. 1020R on the activities of protein phosphatases and protein kinases

Soliev

Hosokawa

Enomoto

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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Pseudoalteromonas sp. strain 1020R produces prodigiosin and its closely related congeners, which differ in the length of their alkyl side chains. These red-pigmented compounds were found to exhibit cytotoxicity against human leukemia cell lines. The compounds also showed dose-dependent inhibitory effects on protein phosphatase 2A and protein tyrosine phosphatase 1B (PTP1B), while remaining relatively inactive against protein kinases, including protein tyrosine kinase, Ca 2+ /calmodulin-dependent protein kinase and protein kinases A and C. Comparative studies of the individual pigmented compounds on PTP1B inhibition showed that as the chain length of the alkyl group at the C-3 position of the compound increased, the inhibitory effect on PTP1B decreased. These results suggest that protein phosphatases but not protein kinases might be involved in the cytotoxicity of the prodigiosin family of compounds against malignant cells.

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Section: Discussionsupporting

confidence: 87%

Effects of prodigiosin family compounds fromPseudoalteromonassp. 1020R on the activities of protein phosphatases and protein kinases

Soliev

Hosokawa

Enomoto

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…In contrast, in presence of 100 nM MAMPDM, expression of p53 in con A stimulated cells was suppressed and its level was marginally higher than that in the unstimulated cells. Arrest of colon cancer cells treated with prodigiosin in G1 phase has been observed independent of p53 [41]. Therefore, the effect of MAMPDM on expression of p53 was more likely to be related to its proliferation suppressive activity.…”

Section: Discussionmentioning

confidence: 96%

Role of interleukin-2 regulated proteins in immunosuppression by the N-alkylated prodigiosin analogue

Pandey

Chander

Sainis

2007

International Immunopharmacology

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“…The planar nitrogens in prodigiosin and its analogs can chelate copper and zinc, and also alter cellular pH (23)(24)(25). In cultured cell lines, prodigiosin can exert effects similar to those of the polyether ionophores salinomycin and nigericin, which inhibit the activity of vacuolar H + -adenosine triphosphatase (V-ATPase) (26). Inhibition of V-ATPase interferes with vesicle acidification, which is necessary for endocytosis and activation of the FZD/LRP6 complex that mediates Wnt signaling (27,28).…”

Section: Discussionmentioning

confidence: 99%

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Wang

Zhou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

166

119

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Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/ β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the lowdensity lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β). In breast cancer MDA-MB-231 and MDA-MB-468 cells, nanomolar concentrations of prodigiosin decreased phosphorylation of LRP6, DVL2, and GSK3β and suppressed β-catenin-stimulated Wnt target gene expression, including expression of cyclin D1. In MDA-MB-231 breast cancer xenografts and MMTV-Wnt1 transgenic mice, administration of prodigiosin slowed tumor progression and reduced the expression of phosphorylated LRP6, phosphorylated and unphosphorylated DVL2, Ser9 phosphorylated GSK3β, active β-catenin, and cyclin D1. Through its ability to inhibit Wnt/β-catenin signaling and reduce cyclin D1 levels, prodigiosin could have therapeutic activity in advanced breast cancers.prodigiosin | Wnt/beta-catenin signaling | breast cancer | LRP6 | Dishevelled (DVL)

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Non-apoptotic concentrations of prodigiosin (H+/Cl− symporter) inhibit the acidification of lysosomes and induce cell cycle blockage in colon cancer cells

Cited by 42 publications

References 28 publications

Effects of prodigiosin family compounds fromPseudoalteromonassp. 1020R on the activities of protein phosphatases and protein kinases

Effects of prodigiosin family compounds fromPseudoalteromonassp. 1020R on the activities of protein phosphatases and protein kinases

Role of interleukin-2 regulated proteins in immunosuppression by the N-alkylated prodigiosin analogue

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

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