A Comparative Study of the Polysialylation Inhibition in the Kelly Neuroblastoma Cell Line by Withania somnifera and Bacopa monnieri Extracts

Nada Ahmad Al-Hasawi

Abstract


Summary. 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 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 a model of human tumour cell line.  Throughout cell lines including; HCT 116 colorectal carcinoma, Kelly neuroblastoma and 1321N1 brain astrocytoma, high PSA signals determined by in-situ immunostaining, were observed in Kelly cell line, thus was used as a model. The crude water and hexane extracts of Withania somnifera roots, at a non-cytotoxic concentration (2.5 mg/ml) as determined by MTT assay, were found to cause < 50 % (p ≤ 0.0096) inhibition of PSA expression as determined by ELISA, compared to same extracts from the Bacopa Monnieri. We proposed a therapeutic approach in which tumour motility can be reduced through inhibition of PSA expression by compounds present in W. somnifera roots without targeting cell survival processes.    

Industrial relevance. Metastases is the major cause of cancer mortality worldwide, despite major improvements in the detection and evaluation of more targeted drugs.  We proposed a new strategy in which metastasis is prevented by maintaining the adhesive properties of cancer cells by blocking their detachment and motility.  This may be achieved with inhibitors of PSA which appears to play an important role in attenuating the adhesive properties of tumour cells. Withania somnifera provides a promising source of such agents as suggested by our results.  Further isolation and purification will be needed to identify the potential bioactive compounds present in Withania somnifera.  This could lead to development of new efficacious anti-metastatic agents that have the advantage of not having any cytotoxicity which can be used in adjuvant therapy in combination with currently used chemotherapeutic agents; indeed it may be possible to lower the doses of these toxic drugs to reduce side effects.

Keywords. Polysialic acid; Neuroblastoma; Kelly cell line; Withania somnifera; Bacopa monnieri


Keywords


Polysialic acid; Neuroblastoma; Kelly cell line; Withania somnifera; Bacopa monnieri

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