Evaluation of marine sponge metabolites for cytotoxicity and signal transduction activity.
Twenty-four metabolites derived from marine sponges were evaluated for their cytotoxicities against two human tumor cell lines, non-small cell lung carcinoma A549 and colon adenocarcinoma HT-29, and against one murine leukemia cell line, P-388, and evaluated for their ability to effect signal transduction in a newly developed cell adhesion assay using an EL-4 cell line. The compounds included latrunculin A [1], batzelline A [2], chondrillin [3], aureol [4], epihippuristanol, theonellamine B, discorhabdins A and C, kabiramide C, dercitin, meridine, manzamines A, B, and C, 8,15-diisocyano-11(20)-amphilectene and the corresponding C-15 formamide, a 20-carbon acetylenic alcohol, 4,5-dihydro-6"-deoxybromotopsentin, epispongiadiol, isospongiadiol, puupehenone, reiswigin A, and demethyl- and demethyloxyaaptamine. Latrunculin A [1], batzelline A [2], chondrillin [3], and aureol [4] expressed the desired profile of a greater than five-fold level of cytotoxicity against A549 relative to P-388, and an effect in the cell adhesion assay. In this group of compounds, cytotoxicity toward A549 was equal to or more pronounced than against HT-29. Latrunculin A was evaluated in an sc-implanted human A549 lung tumor xenograft mouse model and yielded a T/C of 146%. Batzelline A was evaluated in the cancer cell line panel at the National Cancer Institute and found to express selective cytotoxicity against several melanoma cancer cell lines.
Longley
R E
RE
Harbor Branch Oceanographic Institution, Inc. Fort Pierce, Florida 34946.
McConnell
O J
OJ
Essich
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E
Harmody
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D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D007941:Leukemia P388 / Q000473:pathology; D051379:Mice; D011161:Porifera / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011493:Protein Kinase C