Polyacetylene diols with antiproliferative and driving Th1 polarization effects from the marine sponge Callyspongia sp.
A screening of 30 crude extracts of marine sponges against human promyelocytic leukemia cells (HL-60) yielded an EtOAc extract of the sponge Callyspongia sp. (Callyspongiidae) with significant activity. Further bioassay-guided fractionation of the EtOAc extract led to the isolation of three polyacetylene metabolites: a new polyacetylene diol, callyspongidiol (1), along with two known compounds, siphonodiol (2) and 14,15-dihydrosiphonodiol (3). Their structures were determined by a combination of spectroscopic analyses. Compounds 1-3 exhibited antiproliferative activity against HL-60 with IC(50) values of 6.5, 2.8, and 6.5 microg/ml, respectively. These metabolites induce apoptosis in HL-60 cells. Dendritic cells (DC) differentiated with 1-3 enhance the differentiation of naïve T cells towards the Th1 type.
Umeyama
Akemi
A
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. umeyama@ph.bunri-u.ac.jp
Matsuoka
Nanae
N
Mine
Rieko
R
Nakata
Akemi
A
Arimoto
Eri
E
Matsui
Miwa
M
Shoji
Noboru
N
Arihara
Shigenobu
S
Takei
Masao
M
Hashimoto
Toshihiro
T
D000114:Acetylene / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D047128:Callyspongia / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D011108:Polymers / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D053279:Polyynes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018417:Th1 Cells / Q000378:metabolism
C548230:14,15-dihydrosiphonodiol; D000970:Antineoplastic Agents; D011108:Polymers; C548229:callyspongidiol; C504707:tetrahydrosiphonodiol; D053279:Polyynes; D000114:Acetylene