It has been known for several decades that alterations in glycosylation patterns play an important role in the metastasis of cancer cells but thus far few drugs have been developed specifically targeting these molecules. Polysialic acid (PSA) is a developmentally regulated cell-surface glycan consisting of sialic acid monomers attached by α-2,8-glycosidic linkages which, in mammals, is mainly expressed on neural cell adhesion molecule (NCAM). Polysialylated NCAM is abundant in embryonic tissues, and limited to areas of persistence of neuronal plasticity in adults. Up-regulation of PSA has also been reported in highly metastatic cancers where it appears to be associated with tumour progression. In this study we tested the ability of crude extracts of the Ayurvedic medicinal plants, namely Withania somnifera (ashwaghanda) and Bacopa monnieri (Brahmi), to inhibit PSA expression in several human tumour cell lines including TE671 rhabdomyosarcoma, Kelly neuroblastoma, 1321N1 brain astrocytoma and HCT colorectal carcinoma. Highest PSA signals, determined by ELISA, were observed in Kelly cells. Hexane extracts of roots of Withania somnifera, at doses that did not cause any cytotoxicity as determined by MTT assay, were found to cause 20-30% inhibition of PSA expression. To exclude the effect of counteracting constituents, we intend to fractionate the herbal extract to purify and characterise the compounds responsible for this inhibitory activity. We propose a therapeutic approach in which expression of glycans associated with tumour progression and metastasis could be inhibited by prolonged treatment with relatively non-toxic agents that do not target cell survival processes.