RESUMO
Curcumin is a polyphenol pigment product from the rhizome of curcumin longa.It is associated with numerous therapeutic benefits,including antioxidant,anti-inflammatory and anticancer activities.Research shows that EF24 is a curcumin analog that can induce tumor cell apoptosis,arrest cell cycle,inhibit cell invasion and metastasis and has synergistic effect of combined antitumor agents.EF24 has improved anticancer activity and bioavailability against various cancer cell lines over curcumin without increased toxicity.EF24 would have great potential to be used as a useful therapeutic agent for the treatment of various types of cancer.
RESUMO
Objective: To search for the small molecule inhibitor with anti-tumor activity by fibroblast growth factor receptor 1 (FGFR1) as target. Methods: The analogue B6 of EF24 was obtained by reforming mono carbonyl curcumin analogues and applied to identifying the target with FGFR1 kinase activity assay. The effect of EF24 and its analogue B6 on the proliferation of HL7702 in normal human and four tumor cells, such as NCI-H460, SGC-7901, A549, and U251; With the concentration of 2.5, 5, and 10 μmol/L, B6 was used to investigate the phosphorylation inhibition of bFGF/FGFR downstream signal protein expression in NCI-H460 cells and Caspase-3 factor expression. Results: With the FGFR1 as target, B6 could inhibit the phosphorylation of FGFR1 in NCI-H460 cells, AKT, and ERK1/2; It also could inhibit the proliferation of cancer cells and promote cell apoptosis. Conclusion: The analogue B6 of EF24 is obtained from the leading compound EF24 with in vitro anti-tumor effect, which provides the basis of looking for the candidate anti-tumor drugs of FGFR1 inhibitor.
RESUMO
Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.