SYUNZ-16, a newly synthesized alkannin derivative, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of AKT/FOXO signal pathway.

Alkannin is the major bioactive compound of Arnebia euchroma roots, which is used in many therapeutic remedies in Chinese traditional medicine. SYUNZ-16 is a new derivative of alkannin. In this study, anticancer effects of SYUNZ-16 on human lung adenocarcinoma cell line GLC-82 and human hepatocarcinoma cell line Hep3B were tested in vitro. The results showed SYUNZ-16 could obviously inhibit the proliferation of these cancer cell lines via induction of apoptosis, with the evidence of increasing AnnexinV-positive cells and cleaved caspase-3 and PARP fragments. More importantly, we found that SYUNZ-16 could inhibit AKT activity in cell-free system. Treatment of cancer cells with SYUNZ-16 decreased the phosphorylation of AKT. Additionally, SYUNZ-16 partially attenuated the phosphorylation levels of FKHR and FKHRL1 in a dose-dependent and time-dependent fashion, and led to an increase in the nuclear accumulation of exogenous FKHR, and upregulated the mRNA expression of Bim and TRADD in cancer cells. Further study showed that constitutively activated AKT1 transfection could reduce apoptosis induction mediated by SYUNZ-16. The in vivo experiments showed that SYUNZ-16 had inhibitory effects on S-180 sarcoma implanted to mice. And in GLC-82 xenograft models, SYUNZ-16 at 20 mg/kg/qod remarkably inhibited the tumor growth with the T/C value of 45.3%. Taken together, SYUNZ-16 might be a potent inhibitor of AKT signaling pathway in tumor cells. These data provide evidence for the development of SYUNZ-16 as a potential antitumor drug candidate for further research and development.

[Tea polyphenol inhibit on growth of human nasopharyngeal carcinoma cell and xenograft in nude mice].

BACKGROUND AND OBJECTIVE: It was reported that tea polyphenol(TP) possess preventive and anticancer effects on various human cancers. However the report about TP against human nasopharyngeal carcinoma(NPC) was very rare. Our previous studies have also suggested that TP has antiproliferative effect and may induce apoptosis in human NPC cell. In order to further explore the antitumor effect, the authors investigated the growth inhibition effect of TP on various human NPC cell lines and xenograft tumors of human NPC in nude mice. METHOD: Antiproliferative effect of TP against seven human NPC cell lines was tested by MTT method. Antitumor effect of TP was determined using the xenografts models of human NPC cell (CNE2) in nude mice. RESULTS: The fifty percent inhibition concentration (IC50) of TP against NPC cell lines (NPC/HK1, CNE1, CNE2, HNE1, HNE2, SUNE1, and Fadu cells) were calculated to be 55.83, 98.43, 119.21, 127.74, 158.07, 160.72, and 163.59 micrograms/ml, respectively. Average inhibitory rates of TP against xenograft tumors of human NPC in nude mice were 12.7% (P > 0.05), under the dosage of 5 mg.(kg..d)-1, ig x 18 d. Under the dosages of 10 mg.(kg..d)-1, ig x 18 d and 20 mg.(kg..d)-1, ig x 18 average inhibitory rates were 31.0% and 38.5%, (P < 0.01), respectively. CONCLUSION: The results indicated that TP possessed different antiproliferative effect on seven human NPC cell lines in vitro and on xenograft tumor of human NPC in nude mice.