Two-headed sphingolipids bear a certain similarity with sphingolipids in the structure and but differing from classical sphingolipids in alpha,omega-position of the basic groups. We analyzed the apoptotic effects of some two-headed sphingolipids including rhizochalin (Rhz) and its derivatives isolated from sponge Rhizochalina incrustata on human leukemia HL-60 cells. Direct addition of Rhz induced apoptosis of HL-60 cells. The aglycon of Rhz, which has no galactosyl residue, showed a stronger ability to induce apoptotic activity than Rhz. Rhz congeners with acetate derivatives only weakly induced apoptosis. The usual mitochondrial membrane permeability changes and the decrease of protein levels of procaspases-8, -9, and -3 correlated with the apoptotic activity of Rhzs. These results suggest that derivatives of two-headed sphingolipids potently induce apoptosis in mammalian cells when administered exogenously and this cell death was dependent on caspase activation pathways.
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http://dx.doi.org/10.1248/bpb.32.955 | DOI Listing |
J Org Chem
January 2013
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA.
A five-step transformation of D-glucosamine, commencing with indium-mediated Barbier reaction without isolation of intermediates, into (R,R)-2-aminohex-5-ene-1,3-diol in 45-51% is described. The latter is a useful synthon for assembly of L-threo-sphingoid bases: long-chain aminoalkanols and aminoalkanediols with configurations antipodal to that found in mammalian D-erythro-sphingosine but prevalent among invertebrate-derived sphingolipids. The utility of the method is demonstrated by the first total synthesis of rhizochalinin C, the long-chain, "two-headed" sphingoid base aglycon of the natural product rhizochalin C from the marine sponge Rhizochalina incrustata.
View Article and Find Full Text PDFBiol Pharm Bull
June 2012
BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501–759, Republic of Korea.
Rhizochalin is a two-headed sphingolipid-like compound isolated from the sponge Rhizochalina incrustata. It has been reported that rhizocalin and its derivates have a chemopreventive and chemotherapeutic effect. However, the molecular mechanism of these effects is not understood.
View Article and Find Full Text PDFMar Biotechnol (NY)
June 2011
Laboratory of Marine Biochemistry, Pacific Institute of Bioorganic Chemistry, Far East Division of Russian Academy of Sciences, 690022, pr. 100 let Vladivostoku, 159, Vladivostok, Russian Federation.
Previously, we have purified three distinct DNases from spermatozoa of sea urchin Strongylocentrotus intermedius and we suppose the role of Ca(2+), Mg(2+)-dependent DNase (Ca, Mg-DNase) in apoptosis of spermatozoa. Two-headed sphingolipid rhizochalin (Rhz) induced characteristic apoptotic nuclear chromatin changes, internucleosomal DNA cleavage, and activation of caspase-9, caspase-8, and caspase-3 in spermatozoa as was shown by fluorescence Hoechst 33342/PI/FDA analysis, DNA fragmentation assay, and fluorescence caspase inhibitors FAM-LEHD-fmk, FAM-IETD-fmk, and FAM-DEVD-fmk, respectively. Inhibitor of caspase-3 z-DEVD-fmk subdued Rhz-induced internucleosomal ladder formation, which confirmed the major role of caspase-3 in apoptotic DNA cleavage probably through Ca, Mg-DNase activation.
View Article and Find Full Text PDFLipids
September 2009
Pacific Institute of Bioorganic Chemistry, Vladivostok, 690022, Russian Federation.
Rhizochalin [(2R,3R,26R,27R)-2,27-diamino-3-hydroxy-26-[(2R,3R,4S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy]octacosan-11-one], an antimicrobial and cytotoxic marine two-headed sphingolipid-like natural product, isolated from the sponge Rhizochalina incrustata, and some related compounds were studied as anticarcinogenic and proapoptotic agents. The corresponding effects were tested on the mouse skin epidermal JB6 P(+) Cl 41 cell line, its stable transfectants, THP-1, HeLa, and SNU-C4 human tumor cells using a variety of assessments, including cell viability (MTS), flow cytometry, anchorage-independent soft agar, and luciferase assays. At 5-10 muM concentrations, rhizochalin was effective as an inhibitor of the malignant transformation of JB6 P(+) Cl 41 cells or colony formation of human tumor cells, which exerted its action, at least in part, through the induction of p53-dependent apoptosis.
View Article and Find Full Text PDFBiol Pharm Bull
June 2009
Department of Biochemistry, School of Medicine, Dong-A University, Busan, Korea.
Two-headed sphingolipids bear a certain similarity with sphingolipids in the structure and but differing from classical sphingolipids in alpha,omega-position of the basic groups. We analyzed the apoptotic effects of some two-headed sphingolipids including rhizochalin (Rhz) and its derivatives isolated from sponge Rhizochalina incrustata on human leukemia HL-60 cells. Direct addition of Rhz induced apoptosis of HL-60 cells.
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