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Coumalamide derivatives are one of 2-pyrones derivatives, exerting multifunctional bioactivity. An array of coumalamide derivatives have been developed and presented good antiproliferative properties on cancer cells. However, the synthesis of 5-substituted coumalamide derivatives has not yet been published. Resistance to chemotherapeutic drugs is a major obstacle in hepatocellular carcinoma therapy. Recent evidence suggests that overexpression of constitutively active Akt confers on cancer cells resistance to chemotherapy. In this study, we report the synthesis and biological evaluation of a novel N -substituted coumalamide derivative (NSCA-1). The results indicated that NSCA-1 exerts synergistic cytotoxicity with Adriamycin in HepG2/ADR (HepG2/adriamycin) cells. Furthermore, both of the Akt kinase activity and phosphorylated Akt (Ser473) were found to be inhibited by NSCA-1 and subsequently resulting in decreased phosphorylation of GSK-3β. The intracellular accumulation of Adriamycin was also boosted by NSCA-1 via reducing the expression of p-gp. In addition, we found that combined treatment with NSCA-1 enhance cell apoptosis induced by Adriamycin via p53-dependant apoptotic pathway. [ABSTRACT FROM AUTHOR]

Eriocaulon sieboldianum (Sieb. & Zucc. ex Steud.), a genus of Eriocaulon in the Eriocaulaceae family, is an edible and medicinal plant used in traditional Chinese medicine. It was processed into healthcare beverages for expelling wind-heat, protecting eyes, and reducing blood fat. Also, it has been used with other herbs as Traditional Chinese herbal compound to treat cancer as adjuvants in tumor therapy in China. However, the active fractions and precise cellular mechanisms of E. sieboldianum extract remain to be illustrated. The goal of this study was to investigate the effects of the active fraction of E. sieboldianum on the growth of K562 cells and understand the possible mechanisms of its action. Our findings suggested that the fraction E3 of E. sieboldianum could effectively inhibit the activity of Aurora kinase and induce apoptosis via blocking cell cycle, up-regulating the expression of proapoptotic proteins including p53 and Bax and reducing the expression of Bcl-2. The levels of Cytochrome C, cleaved caspase-9, cleaved caspase-3 and cleaved PARP were also found to be increased after treatment with fraction E3 of E. sieboldianum . This study could improve the development of E. sieboldianum and raise its application value in cancer adjuvant therapy. Considering it is both a dietary supplement and a traditional Chinese herbal medicine which exhibits anticancer activities, it can be developed into functional food. [ABSTRACT FROM AUTHOR]