Report: Cytotoxic flavonoids from the young twigs and leaves of Caesalpinia bonduc (Linn) Roxb.

The extraction, fractionation and recognition of flavonoids from the ethanolic extract of young twigs and leaves of C. bonduc were carried out. In addition, cytotoxic study of the flavonoids on two cancer cell lines, BGC-823 and HeLa was carried our using sulphorhodamine B assay. Seven flavonoids, six of which are being reported for the first time in this plant, were isolated. Their structures were identified by MS and NMR spectroscopic methods. Petroleum ether, ethyl acetate and water fractions exhibited moderate cytotoxic activity against HeLa cells. Five compounds showed cytotoxic activity against HeLa cell in comparison with Paclitaxel, while only one compound showed a good degree of cytotoxic activity against BGC-823 cell in comparison to Paclitaxel. The results obtained showed a structure - activity relationship.

Mutation in integrin-linked kinase (ILK(R211A)) and heat-shock protein 70 comprise a broadly cardioprotective complex.

RATIONALE: Integrin-linked kinase (ILK) has been proposed as a novel molecular target that has translational potential in diverse cardiac diseases, since its upregulation promotes a broadly cardioprotective phenotype. However, ILK has been implicated as both a cardioprotective and oncogenic target, which imposes therapeutic constraints that are generally relevant to the translational potential of many kinases. OBJECTIVE: To study the cardioprotective properties of the activation-resistant, non-oncogenic, mutation of ILK (ILK(R211A)) against experimental MI in vivo and Doxorubicin induced apoptosis in vitro and it's relationships to stress induced heat shock proteins. METHODS/RESULTS: The transgenic mouse heart over-expressing a point mutation in the ILK pleckstrin homology (PH) domain (Tg(R211A)) exhibits a highly cardioprotective phenotype based on LAD-ligation-induced MI reduction in vivo, and on protection against doxorubicin (DOX)-induced cardiomyocyte apoptosis when overexpressed in human induced pluripotent stem cell (iPS)-derived cardiomyocytes in vitro. Intriguingly, the degree of cardioprotection seen with the ILK(R211A) mutation exceeded that with the ILK(S343D) mutation. Microarray and immunoprecipitation analyses revealed upregulation of expression levels and specific binding of ILK(WT), ILK(S343D) and ILK(R211A) to both constitutively active heat-shock protein 70 (Hsc70) and inducible Hsp70 in response to MI, and to acute ILK overexpression in iPSC-cardiomyocytes. ILK-mediated cardioprotection was shown to depend upon Hsp70 ATPase activity. CONCLUSIONS: These findings indicate that wild type ILK and the non-oncogenic ILK(R211A) mutation comprise a cardioprotective module with Hsp/c70. These results advance a novel target discovery theme in which kinase mutations can be safely engineered to enhance cardioprotective effects.