Sea urchin embryo model in anti-mitotic drug screening

See our screening results in In_Vivo database and NCI-60 screening results in NCI_tested database in Database Center

Our screening data see in database fields:

effective concentration of compound resulted in alteration of quick successive cell divisions in the early embryo, mmol
effective concentration of compound resulted in total block of quick successive cell divisions in the early embryo, mmol
effective concentration of compound resulted in quick embryo rotation on the bottom of the vessel instead of normal forward swimming, mmol
  1. Semenova, M.; Kiselyov, A.S.; Semenov, V.V. Sea urchin embryo as a model organism for the rapid functional screening of tubulin modulators
  2. Semenova M.N.; Kiselyov A.S.; Titov, I.Y.; Raihstat, M.M.; Molodtsov, M.; Grishchuk, E.; Spiridonov, I.; Semenov, V.V. In Vivo evaluation of indolyl glyoxamides in the sea urchin embryo model: correlation with in vitro tubulin dynamics effects
  3. Semenova M.A., at all A Synthetic Derivative of Plant Allylpolyalkoxybenzenes Induces Selective Loss of Motile Cilia in Sea Urchin Embryos
  4. Kiselyov A.S.; Semenova M.N.; at all Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays
  5. Semenov V.V., Kiselyov A.S; at all Synthesis of Antimitotic Polyalkoxyphenyl Derivatives of Combretastatin Using Plant Allylpolyalkoxybenzenes
  6. Sheremetev A.B., Dmitriev D.E., at all New functionaized aminofurazans as potential antimitotic agents in the sea urchin embryo assay
  7. Semenova M.A., at all; Application of plant allylpolyalkoxybenzenes in synthesis of antimitotic phenstatin analogues; Bioorganic & Medicinal Chemistry Letters

Identification of anti-mitotic molecules that affect tubulin dynamics is a multi-step procedure. It includes in vitro tubulin polymerization assay, studies of a cell-cycle effect and general cytotoxicity assessment. To simplify this lengthy screening protocol, we have introduced and validated an assay system based on the sea urchin embryos. The proposed two-step procedure involves

i) fertilized egg test for mitotic arrest

ii) behavioral assessment of a free-swimming blastulae

In order to validate the assay, we have analyzed the effect of a panel of known anti-proliferative agents on the sea urchin embryo. For all tubulin destabilizing drugs, we observed rapid spinning and lack of forward movement of an embryo.

normal movement
tubulin destabilizing drugs
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Both effects are likely to result from the in vivo microtubule disassembly caused by test molecules. Notably, the described assay yields rapid information on antiproliferative, antimitotic, cytotoxic, and tubulin destabilizing activities of the molecules along with their solubility and permeability potential. Moreover, measured potencies of the test articles correlated well with the reported values in both in vitro and cell-based assays.