Abstract
(3S,14S)-Petrocortyne A, a lipid compound (a C46 polyacetylenic alcohol), from marine sponges (Petrosia sp.) is potently cytotoxic against several solid tumour cells. In this study, we investigated in vitro anti-inflammatory and pro-aggregative effects of petrocortyne A at non-cytotoxic concentrations on various cellular inflammatory phenomena using the macrophage and monocytic cell lines RAW264.7 and U937. Petrocortyne A blocked tumour necrosis factor-α (TNF-α) production strongly and concentration-dependently in lipopolysaccharide (LPS)-activated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)/LPS-treated U937 cells. It also blocked NO production concentration-dependently in LPS- or interferon (IFN)-γ-treated RAW264.7 cells. Among the migration factors tested, the compound selectively blocked the expression of hepatocyte growth factor/scatter factor (HGF/SF). On the other hand, as assessed by a cell-cell adhesion assay, petrocortyne A did not block the activation of adhesion molecules induced by aggregative antibodies to adhesion molecules, but suppressed PMA-induced cell-cell adhesion significantly. Intriguingly, petrocortyne A induced U937 homotypic aggregation following long exposure (2 and 3 days), accompanied by weak induction of pro-aggregative signals such as tyrosine phosphorylation of p132 and phosphorylation of extracellular signal-related kinase 1 and 2 (ERK 1/2). Petrocortyne A may thus inhibit cellular inflammatory processes and immune cell migration to inflamed tissue.
Similar content being viewed by others
References
Adams JC, Clelland JD, Collett GD, Matsumura F, Yamashiro S, Zhang L (1999) Cell-matrix adhesions differentially regulate fascin phosphorylation. Mol Biol Cell 10:4177–4190
Bingham CO 3rd (2002) The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation. J Rheumatol (Suppl) 65:3–9
Cho JY, Yoo ES, Baik KU, Park MH (1999) Eudesmin inhibits tumor necrosis factor-alpha production and T cell proliferation. Arch Pharm Res 22:348–353
Cho JY, Baik KU, Jung JH, Park MH (2000a) In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Pharmacol 398:399–407
Cho JY, Baik KU, Yoo ES, Yoshikawa K, Park MH (2000b) In vitro antiinflammatory effects of neolignan woorenosides from the rhizomes of Coptis japonica. J Nat Prod 63:1205–1209
Cho JY, Fox DA, Horejsi V, Sagawa K, Skubitz KM, Katz DR, Chain B (2001) The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood 98:374–382
Cho JY, Chain BM, Vives J, Horejsi V, Katz DR (2003a) Regulation of CD43-induced U937 homotypic aggregation. Exp Cell Res 290:155–167
Cho JY, Katz DR, Chain BM (2003b) Staurosporine induces rapid homotypic intercellular adhesion of U937 cells via multiple kinase activation. Br J Pharmacol 140:269–276
Cho JY, Skubitz KM, Katz DR, Chain BM (2003c) CD98-dependent homotypic aggregation is associated with translocation of protein kinase Cδ and activation of mitogen-activated protein kinases. Exp Cell Res 286:1–11
Eigler A, Sinha B, Hartmann G, Endres S (1997) Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol Today 18:487–492
Feuerherm AJ, Borset M, Seidel C, Sundan A, Leistad L, Ostensen M, Faxvaag A (2001) Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in rheumatoid arthritis. Scand J Rheumatol 30:229–234
Gallucci S, Provenzano C, Mazzarelli P, Scuderi F, Bartoccioni E (1998) Myoblasts produce IL-6 in response to inflammatory stimuli. Int Immunol 10:267–273
Garcia-Pastor P, Randazzo A, Gomez-Paloma L, Alcaraz MJ, Paya M (1999a) Effects of petrosaspongiolide M, a novel phospholipase A2 inhibitor, on acute and chronic inflammation. J Pharmacol Exp Ther 289:166–172
Garcia Pastor P, De Rosa S, De Giulio A, Paya M, Alcaraz MJ (1999b) Modulation of acute and chronic inflammatory processes by cacospongionolide B, a novel inhibitor of human synovial phospholipase A2. Br J Pharmacol 126:301–311
Gerli R, Paolucci C, Gresele P, Bistoni O, Fiorucci S, Muscat C, Belia S, Bertotto A, Costantini V (1998) Salicylates inhibit adhesion and transmigration of T lymphocytes by preventing integrin activation induced by contact with endothelial cells. Blood 92:2389–2398
Hardy SJ, Robinson BS, Ferrante A, Hii CS, Johnson DW, Poulos A, Murray AW (1995) Polyenoic very-long-chain fatty acids mobilize intracellular calcium from a thapsigargin-insensitive pool in human neutrophils. The relationship between Ca2+ mobilization and superoxide production induced by long- and very-long-chain fatty acids. Biochem J 311:689–697
Holly SP, Larson MK, Parise LV (2000) Multiple roles of integrins in cell motility. Exp Cell Res 261:69–74
Kim JS, Lim YJ, Im KS, Jung JH, Shim CJ, Lee CO, Hong J, Lee H (1999) Cytotoxic polyacetylenes from the marine sponge Petrosia sp. J Nat Prod 62:554–559
Kim DK, Lee MY, Lee HS, Lee DS, Lee JR, Lee BJ, Jung JH (2002a) Polyacetylenes from a marine sponge Petrosia sp. inhibit DNA replication at the level of initiation. Cancer Lett 185:95–101
Kim J, Park EJ (2002b) Cytotoxic anticancer candidates from natural resources. Curr Med Chem Anticancer Agents 2:485–537
Ku H, Meier KE (2000) Phosphorylation of paxillin via ERK mitogen-activated protein kinase cascade in EL4 thymoma cells. J Biol Chem 275:11333–11340
Lee HY, Bae GU, Jung ID, Lee JS, Kim YK, Noh SH, Stracke ML, Park CG, Lee HW, Han JW (2002) Autotaxin promotes motility via G protein-coupled phosphoinositide 3-kinase gamma in human melanoma cells. FEBS Lett 515:137–140
Lee JY, Hannun YA, Obeid LM (1996) Ceramide inactivates cellular protein kinase C alpha. J Biol Chem 271:13169–13174
Lim YJ, Lee CO, Hong J, Kim DK, Im KS, Jung JH (2001) Cytotoxic polyacetylenic alcohols from the marine sponge Petrosia species. J Nat Prod 64:1565–1567
Louie SG, Park B, Yoon H (2003) Biological response modifiers in the management of rheumatoid arthritis. Am J Health Syst Pharm 60:346–355
Lowe JB (2003) Glycan-dependent leukocyte adhesion and recruitment in inflammation. Curr Opin Cell Biol 15:531–538
Lundberg IE (2000) The role of cytokines, chemokines, and adhesion molecules in the pathogenesis of idiopathic inflammatory myopathies. Curr Rheumatol Rep 2:216–224
McCarthy PJ, Pitts TP, Gunawardana GP, Kelly-Borges M, Pomponi SA (1992) Antifungal activity of meridine, a natural product from the marine sponge Corticium sp. J Nat Prod 55:1664–1668
Nambu M, Mayumi M, Mikawa H (1992) Regulation of the expression of leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on a human eosinophilic leukemia cell line EoL-3. Cell Immunol 143:335–347
Payne DN (2003) Nitric oxide in allergic airway inflammation. Curr Opin Allergy Clin Immunol 3:133–137
Posadas I, De Rosa S, Terencio MC, Paya M, Alcaraz MJ (2003) Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor-alpha by inhibiting nuclear factor-kappaB activation. Br J Pharmacol 138:1571–1579
Poupon MF (1995) Cancer metastasis. Bull Cancer 82 (Suppl 2):93s–100s
Randazzo A, Bifulco G, Giannini C, Bucci M, Debitus C, Cirino G, Gomez-Paloma L (2001) Halipeptins A and B: two novel potent anti-inflammatory cyclic depsipeptides from the Vanuatu marine sponge Haliclona species. J Am Chem Soc 123:10870–10876
Rochon YP, Frojmovic MM (1992) A model for the recruitment of neutrophils at sites of inflammation. Physiological relevance of in vivo neutrophil aggregation. Med Hypotheses 38:132–138
Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-alpha expression by adenosine: role of A3 adenosine receptors. J Immunol 156:3435–3442
Sano H, Zhu X, Sano A, Boetticher EE, Shioya T, Jacobs B, Munoz NM, Leff AR (2001) Extracellular signal-regulated kinase 1/2-mediated phosphorylation of cytosolic phospholipase A2 is essential for human eosinophil adhesion to fibronectin. J Immunol 166:3515–3521
Sekut L, Connolly KM (1996) Pathophysiology and regulation of TNF-α in inflammation. Drug News Perspect 9:261–269
Tabata N, Ido M, Suga S, Ohgimoto S, Tsurudome M, Kawano M, Nishio M, Watanabe N, Okamoto K, Komada H, Sakurai M, Ito Y (1997) Protein tyrosine kinase activation provides an early and obligatory signal in anti-FRP-1/CD98/4F2 monoclonal antibody induced cell fusion mediated by HIV gp160. Med Microbiol Immunol (Berl) 186:115–123
Walsh LJ (2003) Mast cells and oral inflammation. Crit Rev Oral Biol Med 14:188–198
Warren AP, Patel K, McConkey DJ, Palacios R (1996) CD98: a type II transmembrane glycoprotein expressed from the beginning of primitive and definitive hematopoiesis may play a critical role in the development of hematopoietic cells. Blood 87:3676–3687
Weeks BS, Iuorno J (1996) Phosphatase inhibitors promote ICAM-1 and LFA-1 mediated homotypic aggregation of Jurkat and U937 cells. Biochem Biophys Res Commun 226:82–87
Acknowledgements
This work was supported in part by New Faculty Member Support Grant 3003187-1-1 (2003260) from Kangwon National University (to J. Y. C.).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hong, S., Kim, S.H., Rhee, M.H. et al. In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges. Naunyn-Schmiedeberg's Arch Pharmacol 368, 448–456 (2003). https://doi.org/10.1007/s00210-003-0848-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-003-0848-7