prostaglandin-d2 and Melanoma

Topics: Animals; Antineoplastic Agents; Blood Coagulation; Blood Platelets; Blood Vessels; Cell Adhesion; Cell Communication; Cells, Cultured; Cricetinae; Cysteine Endopeptidases; Disease Models, Animal; Endopeptidases; Epoprostenol; Humans; Killer Cells, Natural; Lung Neoplasms; Melanoma; Mice; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Platelet Aggregation; Prostaglandin D2; Prostaglandins D; Rabbits; Rats; Thrombocytopenia; Thromboxane-A Synthase

Topics: Alprostadil; Animals; Cell Cycle; Cell Division; Cell Line; Cells, Cultured; Chemical Phenomena; Chemistry; Dinoprostone; DNA; Humans; Leukemia L1210; Melanoma; Prostaglandin D2; Prostaglandins A; Prostaglandins D; Prostaglandins E

The data presented suggest that F1 and F10 cells display an inverse relationship between their levels of metastasis and prostaglandin D2 production. Prostaglandin D2 was able to reduce in vitro aggregation of platelets from C57 black mice. Other prostaglandins that decreased platelet aggregation such as prostacyclin also reduced the metastatic rate. Prostaglandin D2 also reduced macrophage cytotoxicity for B16 target cells in vitro. Interferons stimulated prostaglandin D2 synthesis in F10 cells and reduced lung metastasis. F10 metastasis was not blocked by interferon to the same extent by in vivo treatment as it had been in vitro, suggesting that interferons and other modulators of cell function have broader activity in vivo than simply increasing the level of prostaglandins being produced by metastatic cells. Metastasis can therefore be viewed as being modulated in vivo by several mechanisms that may include platelet aggregation and elimination of metastasized cells by host defenses such as macrophages. Prostaglandins and other naturally occurring modulators of host resistance, such as interferons, appear to affect the metastatic rate of tumor cells. Although prostaglandin D2 is not a common major AA product of most cells and therefore may not operate in all cell systems, the B16 cells may provide a system to address the importance of these mediators and mechanisms in the metastatic process.

Topics: Animals; Cell Line; Cytotoxicity, Immunologic; Immunity, Innate; Indomethacin; Interferons; Killer Cells, Natural; Macrophages; Melanoma; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasm Transplantation; Platelet Aggregation; Prostaglandin D2; Prostaglandins D

The combined incidence of melanoma and non-melanoma skin cancer (NMSC) is greater than the incidence of all other malignancies in the US. Previously, we demonstrated that the endocannabinoid, arachidonoyl-ethanolamide (AEA), was a potent inducer of apoptosis in NMSC. The metabolism of AEA to the prostaglandin, PGD

Topics: Animals; Apoptosis; Caspase 3; Caspase 7; Cell Line, Tumor; Endoplasmic Reticulum Stress; Glutathione; Melanoma; Mice; Oxidative Stress; Prostaglandin D2; Skin Neoplasms; Thioredoxins

Topics: Antigens, Neoplasm; Cell Line, Tumor; Enhancer of Zeste Homolog 2 Protein; Humans; Melanoma; Polycomb Repressive Complex 2; Prostaglandin D2; Tretinoin

Despite new therapeutic approaches, metastatic melanomas still have a poor prognosis. Statins reduce low-density lipoprotein cholesterol and exert anti-inflammatory and anti-proliferative actions. We have recently shown that simvastatin triggers an apoptotic burst in human metastatic melanoma cells by the synthesis of an autocrine factor.. The current in vitro study was performed in human metastatic melanoma cell lines (A375, 518a2) and primary human melanocytes and melanoma cells. The secretome of simvastatin-stressed cells was analysed with two-dimensional difference gel electrophoresis and MS. The signalling pathways involved were analysed at the protein and mRNA level using pharmacological approaches and siRNA technology.. Simvastatin was shown to activate a stress cascade, leading to the synthesis of 15-deoxy-12,14-PGJ2 (15d-PGJ2 ), in a p38- and COX-2-dependent manner. Significant concentrations of 15d-PGJ2 were reached in the medium of melanoma cells, which were sufficient to activate caspase 8 and the mitochondrial pathway of apoptosis. Inhibition of lipocalin-type PGD synthase, a key enzyme for 15d-PGJ2 synthesis, abolished the apoptotic effect of simvastatin. Moreover, 15d-PGJ2 was shown to bind to the fatty acid-binding protein 5 (FABP5), which was up-regulated and predominantly detected in the secretome of simvastatin-stressed cells. Knockdown of FABP5 abolished simvastatin-induced activation of PPAR-γ and amplified the apoptotic response.. We characterized simvastatin-induced activation of the 15d-PGJ2 /FABP5 signalling cascades, which triggered an apoptotic burst in melanoma cells but did not affect primary human melanocytes. These data support the rationale for the pharmacological targeting of 15d-PGJ2 in metastatic melanoma.

Topics: Apoptosis; Autocrine Communication; Caspase 8; Cell Line, Tumor; Cells, Cultured; Fatty Acid-Binding Proteins; Gene Knockdown Techniques; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intramolecular Oxidoreductases; Lipocalins; Melanocytes; Melanoma; Neoplasm Metastasis; Prostaglandin D2; Simvastatin

Peroxisome proliferator-activated receptors (PPARs) have been originally thought to be restricted to lipid metabolism or glucose homeostasis. Recently, evidence is growing that PPARγ ligands have inhibitory effects on tumor growth. To shed light on the potential therapeutic effects on melanoma we tested a panel of PPAR agonists on their ability to block tumor proliferation in vitro. Whereas ciglitazone, troglitazone and WY14643 showed moderate effects on proliferation, 15d-PGJ2 displayed profound anti-tumor activity on four different melanoma cell lines tested. Additionally, 15d-PGJ2 inhibited proliferation of tumor-associated fibroblasts and tube formation of endothelial cells. 15d-PGJ2 induced the tumor suppressor gene p21, a G(2)/M arrest and inhibited tumor cell migration. Shot gun proteome analysis in addition to 2D-gel electrophoresis and immunoprecipitation of A375 melanoma cells suggested that 15d-PGJ2 might exert its effects via modification and/or downregulation of Hsp-90 (heat shock protein 90) and several chaperones. Applying the recently established CPL/MUW database with a panel of defined classification signatures, we demonstrated a regulation of proteins involved in metastasis, transport or protein synthesis including paxillin, angio-associated migratory cell protein or matrix metalloproteinase-2 as confirmed by zymography. Our data revealed for the first time a profound effect of the single compound 15d-PGJ2 on melanoma cells in addition to the tumor-associated microenvironment suggesting synergistic therapeutic efficiency.

Topics: Antineoplastic Agents; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromans; Humans; Melanoma; PPAR gamma; Prostaglandin D2; Proteome; Pyrimidines; Thiazolidinediones; Troglitazone

This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. Alpha-melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD(2) production in these cells without affecting PGE(2). While cAMP pathways may be involved in regulating PGD(2) production, our results suggest that alpha-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This alpha-MSH-mediated effect may be associated with its role as an immune modulator.

Topics: alpha-MSH; Cell Line, Tumor; Cells, Cultured; Cyclic AMP; Cyclooxygenase 1; Humans; Intramolecular Oxidoreductases; Lipocalins; Melanins; Melanocytes; Melanoma; Prostaglandin D2; Prostaglandins D; Skin Neoplasms

Treatments for primary and metastatic melanomas are rarely effective. Even therapeutics such as retinoic acid (RA) that are successfully used to treat several other forms of cancer are ineffective. Recent evidence indicates that the antiproliferative effects of RA are mediated by the transcription factor SOX9 in human cancer cell lines. As we have previously shown that SOX9 is expressed in normal melanocytes, here we investigated SOX9 expression and function in human melanomas. Although SOX9 was expressed in normal human skin, it was increasingly downregulated as melanocytes progressed to the premalignant and then the malignant and metastatic states. Overexpression of SOX9 in both human and mouse melanoma cell lines induced cell cycle arrest by increasing p21 transcription and restored sensitivity to RA by downregulating expression of PRAME, a melanoma antigen. Furthermore, SOX9 overexpression in melanoma cell lines inhibited tumorigenicity both in mice and in a human ex vivo model of melanoma. Treatment of melanoma cell lines with PGD2 increased SOX9 expression and restored sensitivity to RA. Thus, combined treatment with PGD2 and RA substantially decreased tumor growth in human ex vivo and mouse in vivo models of melanoma. The results of our experiments targeting SOX9 provide insight into the pathophysiology of melanoma. Further, the effects of SOX9 on melanoma cell proliferation and RA sensitivity suggest the encouraging possibility of a noncytotoxic approach to the treatment of melanoma.

Topics: Animals; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Down-Regulation; Humans; Melanoma; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Nude; Microphthalmia-Associated Transcription Factor; Nevus; Prostaglandin D2; Skin Neoplasms; SOX9 Transcription Factor; Tretinoin; Up-Regulation

The PPAR-gamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) and ciglitazone, and the PPAR-alpha ligand, WY-14643, were examined for their effects on proliferation and apoptosis of A375 melanoma, DU145 and PC3 prostate cancer, and MB-MDA-231 breast cancer. While 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited proliferation of A375 melanoma, ciglitazone was inactive against this and the other cell lines. Restriction of specific amino acids known to inhibit proliferation and induce apoptosis sensitized all cell lines to ciglitazone, and the combined effects were greater than the individual effects of either treatment. WY-14643 alone or in combination with amino acid deprivation was inactive. Normal fibroblasts were resistant to the treatments.

Topics: Amino Acids; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Immunologic Factors; Ligands; Male; Melanoma; Methionine; Phenylalanine; PPAR gamma; Prostaglandin D2; Prostatic Neoplasms; Thiazolidinediones; Tyrosine

We have isolated and characterized a novel human and rat organic anion transporter subtype, OATP-D. The isolated cDNA from human brain encodes a polypeptide of 710 amino acids (Mr 76,534) with 12 predicted transmembrane domains. The rat clone encodes 710 amino acids (Mr 76,821) with 97.6% amino acid sequence homology with human OATP-D. Human and rat OATP-D have moderate amino acid sequence homology with LST-l/rlst-1, the rat oatp family, the prostaglandin transporter, and moatl/MOAT1/KIAA0880/OATP-B. Phylogenetic tree analysis revealed that OATP-D is branched in a different position from all known organic anion transporters. OATP-D transports prostaglandin E1 (Km 48.5 nM), prostaglandin E2 (Km 55.5 nM), and prostaglandin F2,, suggesting that, functionally, OATP-D encodes a protein that has similar characteristics to those of the prostaglandin transporter. Rat OATP-D also transports prostaglandins. The expression pattern of OATP-D mRNA was abundant mainly in the heart, testis, brain, and some cancer cells. Immunohistochemical analysis further revealed that rat OATP-D is widely expressed in the vascular, renal, and reproductive system at the protein level. These results suggest that OATP-D plays an important role in translocating prostaglandins in specialized tissues and cells.

Topics: Alprostadil; Amino Acid Sequence; Animals; Anions; Blotting, Northern; Brain Chemistry; Burkitt Lymphoma; Dinoprostone; DNA, Complementary; HeLa Cells; HL-60 Cells; Humans; K562 Cells; Leukemia, Lymphoid; Lung Neoplasms; Melanoma; Molecular Sequence Data; Oocytes; Organic Anion Transporters; Rats; RNA, Messenger; Xenopus laevis

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family of ligand-activated transcription factors. PPARgamma ligands have been shown to inhibit the growth of cells from different cancer lineages. This study was designed to evaluate the effects of PPARgamma receptor activation in human melanoma cell lines. The effects of its expression and activation on cell proliferation and apoptosis in human melanoma cell lines (early stage cancer [WM35] and metastatic tumour [A375]) were investigated. Reverse transcription-polymerase chain reaction and Western blot analysis showed that both human melanoma cell lines expressed PPARgamma mRNA and protein. Treatment of cells transfected with the luciferase gene ligated to PPAR response element constructed promoter showed that ciglitazone and prostaglandin J2 (PGJ2), selective ligands for PPARgamma, increased the luciferase activity, proving the induction of the PPARgamma reporter gene. Ciglitazone and PGJ2 inhibited melanoma cell proliferation in a dose-dependent manner. Analysis of the cellular morphology and apoptosis assayed by fluorescence microscopy after incubation of A375 cells with 10 micro M ciglitazone for 24 h indicated that this ligand not only inhibited cell proliferation but also induced apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Division; Cell Line, Tumor; DNA; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Ligands; Luciferases; Melanoma; Microscopy, Fluorescence; Promoter Regions, Genetic; Prostaglandin D2; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Thiazolidinediones; Time Factors; Transcription Factors

Peroxisome proliferator-activated receptor gamma is a member of the nuclear receptor superfamily involved in adipocyte differentiation and glucose homeostasis. There is evidence that peroxisome proliferator-activated receptor gamma may also act as a tumor suppressor. Here, we demonstrate expression of peroxisome proliferator-activated receptor gamma in benign melanocytic naevi, different variants of primary cutaneous melanomas, and melanoma metastases. Peroxisome proliferator-activated receptor gamma protein and peroxisome proliferator-activated receptor gamma1 mRNA were also detected in human melanoma cell lines. The peroxisome proliferator-activated receptor gamma specific agonists 15-deoxy-Delta12,14-prostaglandin J2, troglitazone, and rosiglitazone dose-dependently inhibited cell proliferation in four melanoma cell lines, whereas a specific agonist of peroxisome proliferator-activated receptor alpha had no such effect. At a concentration of 50 microM rosiglitazone, the most potent peroxisome proliferator-activated receptor gamma agonist tested suppressed cell growth by approximately 90%. Apoptosis could be induced in melanoma cell lines by incubation with tumor-necrosis-factor-related apoptosis-inducing ligand. In contrast, the growth inhibitory effect of peroxisome proliferator-activated receptor gamma activation was independent of apoptosis and seemed to occur primarily through induction of cell cycle arrest. Our data indicate that melanoma cell growth may be modulated through peroxisome proliferator-activated receptor gamma.

Topics: Antineoplastic Agents; Apoptosis; Cell Division; Chromans; Dose-Response Relationship, Drug; Fibrinolytic Agents; Gene Expression Regulation, Neoplastic; Humans; Immunologic Factors; Melanoma; Prostaglandin D2; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Rosiglitazone; Skin Neoplasms; Thiazoles; Thiazolidinediones; Transcription Factors; Troglitazone; Tumor Cells, Cultured

The effects of prostaglandins (PGs) on the Cloudman S91 melanoma CCL 53.1 cell line indicate that melanogenesis and proliferation are regulated by separate mechanisms that are not necessarily cyclic AMP (cAMP) dependent. These cells responded to PGE1 and PGE2 in a dose-dependent manner, by an increase of tyrosinase activity and by inhibition of proliferation. PGA1 and PGD2 inhibited cellular proliferation and tyrosinase activity, while PGF2 alpha had no effect after 24 h of treatment. PGE1, but not PGE2 or PGD2, increased cellular cAMP levels after 30 min of treatment. Treatment with 10 micrograms/ml PGE1 inhibited cellular proliferation after 4 h and enhanced tyrosinase activity after 12 h. Tyrosinase stimulation by PGE1 required de novo transcription and translation. Actinomycin D, cycloheximide, and the tyrosinase inhibitor phenylthiocarbamide blocked tyrosinase activation but did not alter the inhibitory effect of PGE1 on proliferation. Dibutyryl cAMP and 3-isobutyl-1-methylxanthine augmented tyrosinase activation by PGE1 without enhancing the inhibitory action of PGE1 on cell growth. Neither blockage nor enhancement of the PGE1 effect on tyrosinase altered the PGE1-induced retardation of proliferation. These results are in marked contrast to the traditional concept that elevation of cAMP levels in melanoma cells necessarily results in stimulation of melanogenesis and inhibition of proliferation. The data presented propose independent and possibly alternative pathways for the regulation of these two cellular events.

Topics: 1-Methyl-3-isobutylxanthine; Alprostadil; Bucladesine; Cell Division; Cycloheximide; Dactinomycin; Dinoprostone; In Vitro Techniques; Melanins; Melanoma; Monophenol Monooxygenase; Prostaglandin D2; Prostaglandins; Prostaglandins A; Prostaglandins D; Prostaglandins E

Our interest in prostaglandins (PGs) as antitumor agents stemmed from the report of Bregman and Meyskens (Cancer Res., 43: 1642-1645, 1983) that PGA1, PGA2, and PGD2 inhibited colony formation by human melanoma cells obtained from fresh biopsies of melanoma patients. We tested several PGs and found that PGA1, PGA2, and PGD2 were the most cytotoxic to L1210 cells in culture. Therefore, we studied these PGs for their effects on growth, cell survival, and cell progression of murine (B16) and human (RPMI7932,SK Mel 28) melanoma cells in culture. Although the three PGs equally inhibited the growth of B16 cells, PGD2 was more inhibitory to RPMI 7932 or SK Mel 28 than PGA1 or PGA2. Similarly the three PGs were almost equally active in inhibiting colony formation by B16 cells. However, against human melanoma cells, PGD2 was much more active than PGA1, whereas PGA2 was inactive. Towards the end of our study, we obtained PGJ2 and found that it was as cytotoxic as PGD2 for L1210 cells but was more lethal for human melanoma cells. The primary effect of all three PGs was to block cell progression from G1 to S. At 2.5 micrograms of PGD2 per ml, the blockade of cells in G1 and normal progression through the other phases resulted in accumulation of 80-90% of the cells in G1. At this dose, there was no inhibition of DNA synthesis, and cells in S progressed apparently normally through S, until all cells were blocked in G1. DNA synthesis was inhibited at 5 micrograms/ml which slowed cell progression through S and accumulated cells in G1. The partial synchronization of cells in G1 may be useful in devising new combinations of PGD2 with antitumor drugs.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle; Cell Survival; Cells, Cultured; DNA, Neoplasm; Humans; Melanoma; Mice; Neoplasm Proteins; Prostaglandin D2; Prostaglandins A; Prostaglandins D; RNA, Neoplasm

Prostaglandin D2 (PGD2) is lethal to murine and human melanoma cells at high doses, but synchronizes cells at G1 at non-toxic doses (2.5 or 5 micrograms/ml). We tested the lethality to B16 mouse melanoma cells of combinations of PGD2 with anticancer drugs. The drugs selected were mostly those used in treating human melanoma: actinomycin D, Bleomycin, BCNU, cis-platin, melphalan, 5-fluorouracil, and 1-beta-D-arabinofuranosylcytosine (ara-C). PGD2 was combined with the drugs according to 3 different protocols: An asynchronous culture was given a long term (24 hr) exposure simultaneously to PGD2 + drug. Combinations with Bleomycin, ara-C or melphalan were additive or slightly antagonistic whereas PGD2 plus actinomycin D was significantly antagonistic. Cells synchronized in G1 by 24 hr PGD2 exposure were then given a short-term (2 hr) treatment with PGD2 + drug. Combinations with cis-platin, Bleomycin, BCNU or 5-fluorouracil were additive or slightly antagonistic, whereas melphalan and actinomycin D combinations were significantly antagonistic. Cells were released from a PGD2-induced G1 block and were exposed to drug at different times during cell progression. Actinomycin D was antagonistic when added immediately after release from the G1 block, but was significantly synergistic when added 10 to 12 hr later. The effect of the combinations cannot be explained by available cell cycle or biochemical information. The antagonism between PGD2 and several of the drugs resembles the "cytoprotective" effect of PGD2 towards various noxious agents.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Survival; Cells, Cultured; Interphase; Melanoma; Mice; Prostaglandin D2; Prostaglandins D

The relative inhibitory potency of prostaglandin A (PGA) and prostaglandin J2 (PGJ2) analogues compared to prostaglandin A1 (PGA1) was determined in a clonogenic assay system. Three human melanoma cell strains (C8146A, C8146C, and C8161), a human melanoma cell line (M1RW5) and a human neuroblastoma cell line (IMR-32) were used. Prostaglandin analogues were screened in the clonogenic assay system and the dose effect curves were analyzed by linear regression utilizing the median effect relationship. The computer-generated 50% and 95% inhibitory doses showed that 15-deoxy-16-hydroxyl-16-vinyl-prostaglandin A2 (DHV-PGA2) was from two- to three-fold more active than PGA1 in inhibiting the clonogenic growth of human melanoma cells. Based on the 50% inhibitory dose, PGJ2 and its analogues were from two to five times more potent than PGA1. The delta 12- and delta 12,14-PGJ2 were the most potent of the prostaglandins tested. However, the 95% inhibitory dose for prostaglandin D2 (PGD2), PGJ2 and its analogues against neuroblastoma did not show any enhancement in activity in comparison to PGA1, suggesting that some tumor specificity in the activity of these analogues may be signified by the neuroblastoma data. Prostaglandins which contained a fluoride substitution at position 11 were also tested for activity. As we previously observed with other analogues which did not contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring, 9 beta, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid and 9 alpha, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid did not inhibit the clonogenic growth of human melanoma cells. Administration s.c. to established human melanoma tumors growing in athymic nude mice caused a significant growth inhibition. The treatment schedules ranged from 1 to 8 days. Injection s.c. of PGA1 at a dose of 40 mg/kg/day resulted in a 20% suppression in tumor growth. Higher doses (100 and 200 mg/kg/day) effected an 80% reduction in tumor growth. The higher doses were associated with reversible toxicities, diarrhea and skin inflammation. Administration of DHV-PGA2 at a dose of 20 mg/kg/day resulted in 40% reduction in tumor growth. The increased in vivo potency of DHV-PGA2 corresponds to the results obtained in the clonogenic assay system.

Topics: Animals; Cell Line; Dose-Response Relationship, Drug; Humans; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Prostaglandin D2; Prostaglandins A, Synthetic; Prostaglandins D; Prostaglandins, Synthetic; Transplantation, Heterologous; Tumor Stem Cell Assay

Prostaglandin D2 was found to be a potent inhibitor of B-16 melanoma cell replication in vitro. The inhibition was dose-dependent between 3x10(-9)M and 3x10(-6)M (IC50 approximately 0.3 microM after 6 days). On a molar basis, PGD2 was a better inhibitor than PGA2 or 16, 16-dimethyl-PGE2-methyl ester (di-M-PGE2) and in higher concentrations (10(-6)-10(-7)M), comparable to retinoic acid. In higher concentrations, PGD2 inhibited DNA, RNA and protein synthesis. The B-16 melanoma cell line which we used synthesized arachidonic acid metabolites which comigrated with PGA2, PGD2, PGE2, and PGF2 alpha on a thin layer chromatography system.

Topics: Animals; Antineoplastic Agents; Cells, Cultured; DNA, Neoplasm; Female; Humans; Melanoma; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Neoplasms, Experimental; Oleic Acid; Oleic Acids; Prostaglandin D2; Prostaglandins; Prostaglandins D; RNA, Neoplasm; Time Factors

The inhibitory effect of various prostaglandin analogues on the anchorage independent growth of murine and human melanoma cells was measured. PGA analogues (which were modified at C-16 and C-18) did not demonstrate any major improvement in activity over PGA alone. These included 16,16-dimethyl PGA1, 16,16-dimethyl-PGA2, 16,16-dimethyl-18-oxa-PGA2 and trans-delta-2-15-alpha acetoxy-16,16-dimethyl-18-oxa-11-deoxy-PGE1-methylester. The thromboxane synthetase inhibitor, U51605, demonstrated weak anti-proliferative activity. PGD2 (with a ketone at C-11 versus C-9 for PGA and PGE) was the most potent prostaglandin tested. Cells from melanoma lines displayed species differences in their sensitivities. PGA1 and PGE1 were the most potent inhibitors of the anchorage independent growth of murine melanoma cells. On human melanoma cells PGD2 was the most active prostaglandin, 2-3 times more potent than PGA1; PGE1 was a very weak inhibitor.

Topics: Alprostadil; Animals; Cell Division; Cells, Cultured; Humans; Melanoma; Mice; Neoplasms, Experimental; Prostaglandin D2; Prostaglandins A; Prostaglandins D; Prostaglandins E; Prostaglandins H