Development and thermodynamic evaluation of novel lipid raft stationary phase chromatography for screening potential antitumor agents

Abstract

Novel lipid raft stationary phase chromatography (LRSC), with lipid rafts that contain abundant tropomyosin-related tyrosine kinase A receptors immobilized on the stationary phase, was developed for a high-throughput screening of potentially active antitumor agents. Lestaurtinib was used as a model compound to determine the operational parameters of the LRSC. Of all the factors considered, the particle size of column packing, the column temperature and the flow rate were of immense importance in determining the performance of the established LRSC system. In order to profoundly comprehend the binding interaction between the model drug and the receptors on the column, thermodynamic studies were employed. The results revealed that the interaction was spontaneous and exothermic, a typical enthalpy-driven process. Additionally, the primary forces were hydrogen bonding and van der Waals forces. In evaluating the applicability of the method, active extracts from Albizziae Cortex were screened out using the LRSC system under the optimized conditions. The bioactive components were successfully confirmed by the MTT assay. In conclusion, it could be said that the LRSC is a good model for screening potential antitumor agents because of its viability, rapid response and scalable features.

Lipid raft biomaterial as a mass screening affinity tool for rapid identification of potential antitumor Chinese herbal medicine

“…This also confirms a different molecular target for Gemcitabine and further strengthened the high selectivity of the affinity system. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 11 bioactive isolates via LRSC analysis, it can be said that the two Chinese herbs had some form of interactions with TrkA receptor as reported in similar studies [18,19].…”

“…For instance, cytotoxic bisdesmosides (Segetoside H and I) from the seeds of Vaccaria segetalis exhibited IC 50 at lower micro-molar level similar to the clinically utilized drug cisplatin against MDA-MB-261 breast cancer cells [23]. It is also likely that the effect could be enhanced on other cancer cells, particularly U251 gliocoma cells from which the LRSC was developed as witness in previous studies [18,19]. Notwithstanding these findings, the results still support the fact that in the absence of commonly employed conventional assays for assessing the viability of cancers.…”

“…Here, we report the use of the novel lipid raft biomaterial chromatography as a mass screening system for rapidly isolating potential antitumor CHM. The biomaterial with an over expressed tropomyosin-related kinase A (TrkA) receptor was prepared as described in our previous studies [18,19]. Then ten (10) different aqueous Chinese herbal extracts were prepared and analysed using the LRSC for their antitumor prospects.…”

Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation

“…Our laboratory has been able to screen periplocymarin with antitumor effect from Cortex periplocae by lipid-raft chromatography, which was found to be linked to the tyrosine kinase receptor [6]. It has been reported that periplocymarin strongly inhibited proliferation of PC3, U937, HCT-8, Bel-7402, BGC823, A549 and A2780 cell lines in vitro with IC 50 values of 0.02–0.29 μM [7].…”

Screening Bioactive Compounds of Siraitia grosvenorii by Immobilized β2-Adrenergic Receptor Chromatography and Druggability Evaluation

“…Wang et al (2000) utilized immobilized human serum albumin to screen the bioactive compounds from Artemisia capillaris and confirmed two strong retention peaks of scoparone and capillarisin. Tong et al (2014) extracted lipid rafts from brain glioma U251 cells by synthesizing immobilized lipid to screen for anti-tumor bioactive compounds from Galla chinensis . Despite their great contribution to promote the development of TCM-guided drugs, the aforementioned reports appear to have certain limitations, like lower separating capacity and specificity.…”