Sceptrin, a marine natural compound, inhibits cell motility in a variety of cancer cell lines.
Sceptrin, a natural compound produced by various marine sponges, was tested for its effect on cell motility. We report for the first time that sceptrin inhibits cell motility in several cancer cell lines. The compound shows no toxicity at concentrations that are double the amount of sceptrin required for maximal inhibitory effect. Both random and factor-induced migration were impaired, suggesting that sceptrin targets a central process of cell motility machinery. Activity of de novo synthesized sceptrin was indistinguishable from sceptrin purified from Agelas nakamurai, and the inhibitory activity was found to be, at least partially, due to sceptrin's capability to inhibit cell contractility. Additionally, sceptrin was found to bind to monomeric actin, further suggesting a mechanism involving the actin cytoskeleton. Close analogues of sceptrin were synthesized, tested for their effect on cell motility, and found to be either equimolar or less potent compared to the parental compound. Inadvertent cell motility is a key contributing factor in various human diseases, including cancer and chronic inflammation. Marine compounds isolated from sponges have been proven to be an excellent source of metabolites that show biological activities. Given the recently achieved total synthesis of sceptrin in multigram quantities, sceptrin could prove to be an attractive lead molecule for further preclinical testing and development for therapeutic purposes, as well as a useful research tool to elucidate the mechanisms involved in cell motility.
Cipres
Angel
A
Cancer Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Rd., La Jolla, California, USA.
O'Malley
Daniel P
DP
Li
Ke
K
Finlay
Darren
D
Baran
Phil S
PS
Vuori
Kristiina
K
D047230:Agelas / Q000737:chemistry; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D011554:Pseudopodia / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*
D001688:Biological Products; D011758:Pyrroles; C077210:sceptrin