Phospholipase A2 expression in tumours: a target for therapeutic intervention?

Laye, Jonathan P.; Gill, Jason H.

doi:10.1016/s1359-6446(03)02754-5

Cited by 118 publications

(108 citation statements)

References 55 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…Human sPLA 2 s have been classified into groups IB, IIA, IID, IIE, IIF, III, V, X, XIIA and XIIB according to their structural properties (Laye and Gill, 2003;Rouault et al, 2003;Murakami et al, 2005;Cummings, 2007). Several of these proteins have recently been proposed either as biomarkers of pathologies (Smith et al, 2003;Mallat et al, 2005;Wootton et al, 2007) or as therapeutic targets (Laye and Gill, 2003;Cummings, 2007;Henderson et al, 2007). These enzymes have the capacity to generate biologically active lipid mediators such as lysophosphatidic acid (LPA) and arachidonic acid (AA), which can be further converted into prostaglandin E 2 (PGE 2 ).…”

mentioning

confidence: 99%

“…These enzymes have the capacity to generate biologically active lipid mediators such as lysophosphatidic acid (LPA) and arachidonic acid (AA), which can be further converted into prostaglandin E 2 (PGE 2 ). These lipid mediators are known to be involved in cell proliferation, cell migration, angiogenesis, and are likely to play a role in the initiation and/or progression of colorectal cancer (Morioka et al, 2000;Krause and DuBois, 2001;Laye and Gill, 2003;Mills and Moolenaar, 2003;Murakami et al, 2005). AA can also participate in apoptosis by activating sphingomyelinases and ceramide production (Dong et al, 2005;Ilsley et al, 2005).…”

mentioning

confidence: 99%

“…Secreted phospholipases A 2 have been recently proposed as targets for anticancer drugs (Laye and Gill, 2003;Cummings, 2007), and there is increasing evidence for their involvement in various human cancers. Indeed, the expression levels of sPLA 2 -V and sPLA 2 -X are modified in human lung cancer (Masuda et al, 2005b), and those of sPLA 2 -V and sPLA 2 -XIIA in human ovarian cancer (Gorovetz et al, 2006).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

Wendum

Greenspan

et al. 2008

Br J Cancer

View full text Add to dashboard Cite

Recent studies suggest that secreted phospholipases A 2 (sPLA 2 s) represent attractive potential tumour biomarkers and therapeutic targets for various cancers. As a first step to address this issue in human colorectal cancer, we examined the expression of the full set of sPLA 2 s in sporadic adenocarcinomas and normal matched mucosa from 21 patients by quantitative PCR and immunohistochemistry. In normal colon, PLA2G2A and PLA2G12A were expressed at high levels, PLA2G2D, PLA2G5, PLA2G10 and PLA2G12B at moderate levels, and PLA2G1B, PLA2G2F and PLA2G3 at low levels. In adenocarcinomas from left and right colon, the expression of PLA2G3 was increased by up to 40-fold, while that of PLA2G2D and PLA2G5 was decreased by up to 23-and 14-fold. The variations of expression for sPLA 2 -IID, sPLA 2 -III and sPLA 2 -V were confirmed at the protein level. The expression pattern of these sPLA 2 s appeared to be linked respectively to the overexpression of interleukin-8, defensin a6, survivin and matrilysin, and downregulation of SFRP-1 and RLPA-1, all these genes being associated to colon cancer. This original sPLA 2 profile observed in adenocarcinomas highlights the potential role of certain sPLA 2 s in colon cancer and suggests that sPLA 2 -III might be a good candidate as a novel biomarker for both left and right colon cancers.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

Wendum

Greenspan

et al. 2008

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…The link between PLA 2 and cancer makes these enzymes potential anti-cancer targets (reviewed in Cummings, 2007;Marks et al, 2000;Wang and Dubois,2006). Although a broad range of PLA 2 inhibitors exist (reviewed in Farooqui et al, 1999;Kokotou et al, 2017;Meyer et al, 2005), current knowledge about the mode of action or toxicity in humans or animal models is limited and their effectiveness as pharmacological agents has yet to be addressed (reviewed in Cummings, 2007;Laye and Gill, 2003). A main drawback in targeting PLA 2 with chemotherapeutics is the wide range of individual PLA 2 isoforms, as well as their physiological roles in healthy cell homeostasis (reviewed in Balsinde et al, 1999;Cummings, 2007).…”

Section: Phospholipases As Targets For Chemotherapeuticsmentioning

confidence: 99%

Phospholipases during membrane dynamics in malaria parasites

Flammersfeld

Lang

Flieger

et al. 2018

International Journal of Medical Microbiology

View full text Add to dashboard Cite

A B S T R A C TPlasmodium parasites, the causative agents of malaria, display a well-regulated lipid metabolism required to ensure their survival in the human host as well as in the mosquito vector. The fine-tuning of lipid metabolic pathways is particularly important for the parasites during the rapid erythrocytic infection cycles, and thus enzymes involved in lipid metabolic processes represent prime targets for malaria chemotherapeutics. While plasmodial enzymes involved in lipid synthesis and acquisition have been studied in the past, to date not much is known about the roles of phospholipases for proliferation and transmission of the malaria parasite. These phospholipid-hydrolyzing esterases are crucial for membrane dynamics during host cell infection and egress by the parasite as well as for replication and cell signaling, and thus they are considered important virulence factors. In this review, we provide a comprehensive bioinformatic analysis of plasmodial phospholipases identified to date. We further summarize previous findings on the lipid metabolism of Plasmodium, highlight the roles of phospholipases during parasite life-cycle progression, and discuss the plasmodial phospholipases as potential targets for malaria therapy.

show abstract

“…It is not clear if this enzyme serves as a tumour suppressor or tumour promotor. 29 In a previous paper, starting from our lead compound I 30,31 ( Fig. 1), we designed and synthesized piperazinic derivatives II and III 32 which were specific group II versus group I sPLA 2 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design of new potent and selective secretory phospholipase A2 inhibitors. 6-Synthesis, structure–activity relationships and molecular modelling of 1-substituted-4-[4,5-dihydro-1,2,4-(4H)-oxadiazol-5-one-3-yl(methyl)]-functionalized aryl piperazin/one/dione derivatives

Meddad-Belhabich

Aoun

Djimdé

et al. 2010

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

a b s t r a c tThe group IIA human non-pancreatic secretory phospholipase A 2 (hnp-sPLA 2 ) is one of the enzymes implied in the inflammatory process. In the course of our work on inhibitors of this enzyme we investigated the influence of rigidity of the piperazine region on the biological activity. Several modifications were explored. Various linkers, such as amide, urea, carbamate, or alkoxyphenyl were inserted between the piperazine and the lipophilic chain. Also, modification of the piperazine core to incorporate carbonyl groups was studied. In an in vitro fluorimetric assay using the human GIIA (HPLA 2 ) and porcine pancreatic GIB enzymes, compound 60a (Y = phenoxy, R = C 18 H 37 , Z = CH 2 ) had the optimal activity with an IC 50 = 30 nM on HPLA 2 . By means of molecular modelling we attempted to get informations towards comprehension of differences in activity.

show abstract

Phospholipase A2 expression in tumours: a target for therapeutic intervention?

Cited by 118 publications

References 55 publications

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

Phospholipases during membrane dynamics in malaria parasites

Design of new potent and selective secretory phospholipase A2 inhibitors. 6-Synthesis, structure–activity relationships and molecular modelling of 1-substituted-4-[4,5-dihydro-1,2,4-(4H)-oxadiazol-5-one-3-yl(methyl)]-functionalized aryl piperazin/one/dione derivatives

Contact Info

Product

Resources

About