Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide

Dibenzyl trisulphide (DTS), a main lipophilic compound in Petiveria alloiac ea L. (Phytolaccaceae), was identified as one of the active immunomodulator y compounds in extracts of the plant. To learn more about its biological ac tivities and molecular mechanisms, we conducted one-dimensional NMR interac tion studies with bovine serum albumin (BSA) and tested DTS and related com pounds in two well-established neuronal cell-and-tissue culture systems. We found that DTS preferentially binds to an aromatic region of BSA which is rich in tyrosyl residues. In SH-SY5Y neuroblastoma cells, DTS attenuates th e dephosphorylation of tyrosyl residues of MAP kinase (erk1/erk2). In the s ame neuroblastoma cell line and in Wistar 38 human lung fibroblasts. DTS ca uses a reversible disassembly of microtubules, but it did not affect actin dynamics. Probably due to the disruption of the microtubule dynamics, DTS a lso inhibits neuroblastoma cell proliferation and neurite outgrowth from sp inal cord explants. Related dibenzyl compounds with none, one, or two sulph ur atoms were found to be significantly less effective. These data confirme d that the natural compound DTS has a diverse spectrum of biological proper ties, including cytostatic and neurotoxic actions in addition to immunomodu latory activities. (C) 2001 Elsevier Science BN. All rights reserved.