Antineoplastic activity in vitro of free and liposomal alkylphosphocholines

Zeisig, Reiner; Jungmann, S; Arndt, Dieter; A, Schütt; Nissen, E

doi:10.1097/00001813-199302000-00008

Cited by 21 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When APLs are used in liposomal formulations (e.g., co‐formulated with cholesterol and 1,2‐dipalmitoyl‐ sn ‐glycero‐phosphoglycerol), lysis of red blood cells can be partly prevented . This however is accompanied by a significant reduction in the antitumor activity of the compound, as previously shown in vitro . In serum‐free conditions, the lytic concentration for various APLs and related compounds generally corresponds well to their CMC .…”

Section: Resultssupporting

confidence: 57%

Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy

Gaillard

Seguin

Rémy

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

Sixteen cationic prodrugs of the antitumora lkylphospholipid (APL) erufosine were rationally synthesized to provideo riginal gene delivery reagents with improvedc ytotoxicityp rofile. The DNA complexationp roperties of these cationic lipids were determined and associated transfection rates were measured. Furthermore, the self-assembly properties of the pro-erufosine compounds were investigated and their criticala ggregation concentration was determined. Their hydrolytic stability underp Hc onditions mimickingt he extracellulare nvironment and the late endosome milieu was measured. Hemolytic activity and cytotoxicityo ft he compoundsw ere investigated. The results obtained in various cell lines demonstrate that the prodrugs of erufosined isplay antineoplastic activity similar to that of the parent antitumor drug but are not associated with hemolytic toxicity,w hich is ad ose-limiting side effect of APLs and am ajor obstacle to their use in anticancer therapeutic regimen. Furthermore, by using lipoplexes prepared from ap rodrug of erufosine and a plasmid DNAe ncoding ap ro-apoptotic protein (TRAIL), evidencew as provided for selective cytotoxicityt owards tumor cells while nontumorc ells were resistant. This study demonstratest hat the combination approachi nvolving well tolerated erufosine cationic prodrugs and cancerg ene therapy holds significant promiseint umor therapy.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

show abstract

Section: Resultssupporting

confidence: 57%

Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy

Gaillard

Seguin

Rémy

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Preparation of multilamellar vesicles (MLVs) for L‐HPC was carried out according to the protocol of Zeisig et al (3). Briefly, HPC was dissolved in a chloroform/methanol mixture (7:1) at a concentration of 10 mM.…”

Section: Methodsmentioning

confidence: 99%

“…Hexadecylphosphocholine (HPC) belongs to a group of ether lipids, alkylphosphocholines (APCs), which generated interest in cancer research because of its antitumor effects and its wide spectrum of biological activities. APCs have been demonstrated to possess antineoplastic properties both in experimental studies and clinical trials (1–5). HPC, registered under the brand name Miltefosin® in Germany, has been studied in a number of investigations aiming at the clarification of its mode of action.…”

Section: Introductionmentioning

confidence: 99%

Hexadecylphosphocholine selectively upregulates expression of intracellular adhesion molecule‐1 and class I major histocompatibility complex antigen in human monocytes

Eue¹

2002

J Exp Therapeutics

View full text Add to dashboard Cite

U 937 cells are widely used as a model system to study human monocytes, since they express typical human monocyte markers and properties. Hexadecylphosphocholine (HPC) is the main representative of a class of synthetic phospholipids, the alkylphosphocholines (APCs), and is able to form stable multilamellar vesicles (MLVs = liposomes) to deliver HPC to monocytes/macrophages. Here we report the ability of both micellar and liposomal HPC (L-HPC) to interact with human monocytes and upregulate specific adhesion molecules. Whereas CD14 could neither be induced by HPC nor by L-HPC on U 937 cells, intracellular adhesion molecule-1 and class 1 major histocompatibility complex (MHC-1) antigen were upregulated by both HPC and L-HPC in a dose-dependent manner. These data support and complete previous studies on HPC-induced activation of U 937 cells and provide additional mechanistic information on the initial steps of HPC-mediated recruitment of macrophages and their antitumor activity.

show abstract

“…By direct action, these compounds were shown to influence membrane fluidity, 27 inhibit protein kinase C, 28 modulate phosphatidylcholine biosythesis, 29 inhibit phospholipase, 30 elevate intracellular calcium concentration, 31 regulate signal transduction 32 and inhibit tumor cell growth either in vitro or in vivo. 1,21,[33][34][35][36] As for the indirect effects, these substances have been reported to induce tumor cell differentiation and differentiation of myelomonocytic cells [13][14][15] and to activate macrophages. 10,16,17,[37][38][39] Since most of the studies dealing with HPC-mediated macrophage activation were performed in vitro, it was unclear until now in how far this mechanism substantially contributes to the antitumor effect that has been observed in several human tumor models.…”

Section: Discussionmentioning

confidence: 99%

“…Liposome preparation was carried out as previously described. 16,21 HBSS liposomes for control experiments were prepared as described by Kumar et al 22 Eagle's minimum essential medium (EMEM), Hank's balanced salt solution (HBSS) and fetal bovine serum (FBS) were purchased from Life Technologies (Grand Island, NY). Recombinant mouse IFN␥ (specific activity 1 ϫ 10 5 U/mg protein) was obtained from Genentech (San Francisco, CA).…”

Section: Reagents and Liposome Preparationmentioning

confidence: 99%

Growth inhibition of human mammary carcinoma by liposomal hexadecylphosphocholine: Participation of activated macrophages in the antitumor mechanism

Eue

2001

Int. J. Cancer

View full text Add to dashboard Cite

This study was undertaken to investigate the antitumor effect of liposomal hexadecylphosphocholine (L-HPC), a synthetic phospholipid encapsulated into multilamellar vesicles (MLV). The effect of these liposomes was tested in an orthotopic nude mouse model using the human mammary carcinomas MDA-MB 435 and 231. The main interest of the investigation was to study whether activated macrophages are substantially involved in the tumor growth inhibition mechanism. The growth of both MDA-MB 435 and 231 tumors in the mammary fat pad was significantly inhibited by a 14-day intraperitoneal therapy with L-HPC. The remaining tumors were shown to be heavily infiltrated with macrophages. In vitro studies of mPEM demonstrated a significant induction of macrophage-mediated tumor cytotoxicity (MMCTX) against the 2 cell lines by L-HPC. The L-HPC-mediated activation mechanism was characterized to be IL-6 and TNF␣ dependent but rather independent of IL-1␣ and nitric oxide (NO). NMA, a specific inhibitor of NO production, did not inhibit L-HPC-induced MMCTX. Furthermore, L-HPC was shown to upregulate the matrixmetalloproteinases MMP-9 and MMP-2 secretion into the supernatant. Considering cytokine release and production of collagenases, the L-HPC-induced macrophage activation cascade is assumed to be comparable with that of classical activators such as lipopolysaccharide (LPS) and interferon (IFN) ␥. As far as NO production is considered, the L-HPC activation mechanism differs from that caused by LPS and IFN ␥.

show abstract

Antineoplastic activity in vitro of free and liposomal alkylphosphocholines

Cited by 21 publications

References 0 publications

Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy

Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy

Hexadecylphosphocholine selectively upregulates expression of intracellular adhesion molecule‐1 and class I major histocompatibility complex antigen in human monocytes

Growth inhibition of human mammary carcinoma by liposomal hexadecylphosphocholine: Participation of activated macrophages in the antitumor mechanism

Contact Info

Product

Resources

About