The G-quadruplex ligand, SYUIQ-FM05, targets proto-oncogene c-kit transcription and induces apoptosis in K562 cells.

CONTEXT: N'-(7-Fluoro-5-N-methyl-10H-indolo[3,2-b]quinolin-5-ium)-N,N-dimethylpropane-1,3-diamine iodide (SYUIQ-FM05) is a semi-synthetic derivative of cryptolepine which is from Cryptolepis sanguinolenta (Lindl.) Schlechter (Periplocaeae). This ligand inhibits telomerase activity by stabilizing the G-quadruplex structure and induces growth arrest in cancer cells. OBJECTIVE: The anticancer activity of SYUIQ-FM05 via inhibiting c-kit transcription was investigated in leukemic cells. MATERIALS AND METHODS: The cytotoxicity of SYUIQ-FM05 in K562 cells was evaluated using a cell viability assay and flow cytometry (FCM) at 0.4, 2.0, 10.0 and 20.0 nM. Under the same concentrations of SYUIQ-FM05 or 100 nM imatinib mesylate (IM), quantitative polymerase chain reaction (Q-PCR) investigated transcription of c-kit and bcl-2, and western blotting analyzed the expression levels of c-Kit, total mitogen-activated protein kinase kinases (MEKs), phospho-MEK (p-MEK), total extracellular regulated protein kinases (ERKs), phospho-ERK (p-ERK), Bcl-2 and Bax. RESULTS: SYUIQ-FM05 inhibited cellular growth with an IC(50) of 10.83 ± 0.05 nM in K562 cells. c-Kit transcription was suppressed 2.69-, 4.39-, 7.71- and 10.52-fold at 0.4, 2.0, 10.0 and 20.0 nM SYUIQ-FM05, respectively, which produced proportional loss of total c-Kit protein except IM. Both SYUIQ-FM05 and IM downregulated p-MEK and p-ERK. Furthermore, bcl-2 transcription was suppressed 1.58- and 1.86-fold at 10.0 and 20.0 nM SYUIQ-FM05, respectively, but 0.4 and 2.0 nM SYUIQ-FM05 had no effect. A decrease in Bcl-2 and an increase in Bax appeared in these treated cells. DISCUSSION AND CONCLUSION: These findings demonstrate that SYUIQ-FM05 could induce apoptosis in a leukemic cell line through inhibiting c-kit transcription, which supports the anticancer potency of SYUIQ-FM05 in c-Kit-positive leukemic cells.

[Improvement effects of puerarin on glycated brain damages in rats induced by D-galactose].

OBJECTIVE: To observe the improvement effects of puerarin on glycated brain damages in rat model induced by D-galactose. METHOD: The model rats of protein glycation were induced by intraperitoneal administration of D-galactose (150 mg x kg(-1) x d(-1)) for 8 weeks, and all rats were treated with puerarin (high dose 300 mg x kg(-1), middle dose 150 mg x kg(-1), low dose 75 mg x kg(-1)) for 6 weeks. The activity of aldose reductase in red blood cells, the amount of glycated products (fructosamine in serum, glycohaemoglobin, advanced glycation end-products) and AGEs in brain tissue, calcium ion in brain cells were measured. Moreover, mitochondria in brain hippocampus cells were observed under electronic microscope. RESULT: High dose and middle dose of puerarin can decrease the activity of aldose reductase in red blood cells (P < 0.01), and inhibit the formation of glycation products significantly in model rats induced by D-galactose (P < 0.01). Also, puerarin can decrease the content of AGEs in brain and the level of calcium ions in brain cells (P < 0.05, P < 0.01), and decrease lesions degree in mitochondria in brain hippocampus cells. CONCLUSION: Puerarin can produce the protective effects on glycated brain damages through inhibiting the glycation reaction in rats induced by D-galactose.