Secondary Metabolites from Marine Cyanobacteria and Algae Inhibit LFA-1/ICAM-1 Mediated Cell Adhesion

Abstract

An assay for inhibitors of LFA-1/ICAM-1 mediated cell-cell adhesion has been employed to identify new pharmacologically active compounds from marine cyanobacteria and algae. From a panel of sixty unusual marine natural products, seventeen compounds inhibited LFA-1/ICAM-1-based cell aggregation without showing significant cytotoxicity in the primary assay. Six compounds inhibited the cell-cell adhesion of HL-60 cells to CHO-ICAM-1 cells. The unusual oxylipin Cymathere aldehyde methyl ester (IC (50) 3.5 microM), cyanobacterial lipopeptides microcolins B (IC (50) 0.15 microM) and D (IC (50) 0.9 microM), bromophenol avrainvilleol (IC (50) 2.2 microM), sesquiterpene cymopol (IC (50) 2.7 microM), and cryptophyte derived compound styrylchromone hormothamnione diacetate (IC (50) 1.5 microM) significantly inhibited LFA-1/ICAM-1 mediated cell adhesion. The pharmacological activity and structure-activity relationships of selected marine algal metabolites are described. Abbreviations. LFA-1:Lymphocyte function-associated molecule-1 ICAM-1:Intercellular cell adhesion molecule-1 PMA:Phorbol 12-myristate 13-acetate HL-60:Promyelocytic human leukemia-60 CHO:Chinese hamster ovary

Cytotoxicity of Algae Extracts on Normal and Malignant Cells

“…Furthermore, use of extracts does not allow for determination of components or secondary metabolites, which might be responsible for the effects seen. For example, secondary metabolites of various algae have been found to affect cell adhesion [31]. In other cases, polysaccharide or deacetylated components have been responsible for activities reported [20].…”

[Retracted] Styrylchromones: Biological Activities and Structure‐Activity Relationship

“…Takamatsu and co-workers [ 52 ] evaluated the profile of hormothamnione ( 3 , Figure 34 ) and hormothamnione diacetate ( 33 , Figure 34 ) as inhibitors of the adhesion of HL-60 cells to Chinese hamster ovary (CHO)-ICAM-1 cells through LFA-1/ICAM-1 interaction. LFA-1 is a leukocyte integrin adhesion molecule which promotes intercellular adhesion of most leukocytes to each other and to other cells, playing a crucial role in immunological and inflammatory reactions [ 52 , 53 ]. ICAM-1 is a glycosylated integral membrane protein, that is expressed by most tissues at low levels.…”

“…ICAM-1 plays an important role in inflammation and in T-cell-mediated host defence system. LFA-1 typically binds to ICAM-1, and this interaction mediates a cell adhesion pathway that is important in the progression of inflammatory response [ 52 , 53 ]. In this study, the expression of LFA-1 occurred in HL-60 cells, while CHO-ICAM-1 cells express high levels of ICAM-1.…”

“…Cytochalasin B was used as positive control and showed to inhibit cell adhesion of HL-60 to CHO-ICAM-1 cells with an IC 50 value of 1.2 ± 0.2 μ M. The difference between the results obtained for 2-SC 3 and 33 , regarding the inhibition of cell-cell adhesion, may be attributed to the −OCOCH 3 present at C-3′ and C-5′ on the B-ring of 2-SC 33 , whereas 2-SC 3 has −OH at the same positions. Thus, as 2-SC 33 inhibited cell-cell adhesion between HL-60 cells and CHO-ICAM-1 cell, it may prove to be beneficial in the treatment of inflammation [ 52 ].…”

Naturally occurring cell adhesion inhibitors

“…The unusual oxylipin Cymathere aldehyde methyl ester ( 80 ; IC 50 3.5 µM), cyanobacterial lipopeptide microcolins B ( 81 ; IC 50 0.15 µM) and D ( 82 ; IC 50 0.9 µM), bromophenol avrainvilleol ( 83 ; IC 50 2.2 µM), sesquiterpene cymopol ( 84 ; IC 50 2.7 µM) and cryptophyte-derived compound styrylchromone hormothamnione diacetate ( 85 ; IC 50 1.5 µM) significantly inhibited LFA-1/ICAM-1-mediated cell adhesion (Table 2 ). The pharmacological activity and structure–activity relationships of selected marine algal metabolites are described [ 81 ].…”