EGCG inhibits growth of tumoral lesions on lip and tongue of K-Ras transgenic mice through the Notch pathway.

Epigallocatechin-3-gallate (EGCG), the main active ingredient of green tea, exhibits low toxic side effect and versatile bioactivities, and its anti-cancer effect has been extensively studied. Most of the studies used cancer cell lines and xenograft models. However, whether EGCG can prevent tumor onset after cancer-associated mutations occur is still controversial. In the present study, Krt14-cre/ERT-Kras transgenic mice were developed and the expression of K-RasG12D was induced by tamoxifen. Two weeks after induction, the K-Ras mutant mice developed exophytic tumoral lesions on the lips and tongues, with significant activation of Notch signaling pathway. Administration of EGCG effectively delayed the time of appearance, decreased the size and weight of tumoral lesions, relieved heterotypic hyperplasia of tumoral lesions, and prolonged the life of the mice. The Notch signaling pathway was significantly inhibited by EGCG in the tumoral lesions. Furthermore, EGCG significantly induced cell apoptosis and inhibited the proliferation of tongue cancer cells by blocking the activation of Notch signaling pathway. Taken together, these results indicate EGCG as an effective chemotherapeutic agent for tongue cancer by targeting Notch pathway.

Multifunctional Quaternary Phosphorus/Bromoargentate Hybrids: The Achievement of Greenish Blue Luminescence, Repeatable Photocurrent Responses and Durable Antimicrobial Activities with Enhanced Water Stability.

BACKGROUND: The realization of multifunction in one bulk material is fascinating for developing a new generation of devices. Quaternary phosphorus salts were seldom utilized as templates in haloargentate systems, and the hybridization of alkyl(triphenyl)phosphonium with halometallate will be a good strategy for the development of multifunctional material, especially for biological material. METHODS: Under the template of (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 3, 4), three bromoargentate hybrids were constructed via the solution method, ie, (1,2-DBTPP)(Ag2Br4) (1), {(1,3-DBTPP)2(Ag7Br11)]∙CH3CN∙H2O} n (2), and {[(1,4-DBTPP)(Ag5Br7)](CH3CN)2∙H2O} n (3) (1,2-DBTPP2+=ethane-1,2-diylbis (triphenyl)phosphonium, 1,3-DBTPP2+=propane-1,3-diylbis (triphenyl)phosphonium, 1,4-DBTPP2+=butane-1,4-diylbis (triphenyl)phosphonium)). RESULTS: The (Ag7Br11) n 4n- chain in 2 is a new type of 1-D bromoargentate chain constructed from cubane-like Ag4Br4 nodes, AgBr4 tetrahedrons and AgBr3 triangles. Interestingly, by elongating spacer n from 2 to 4, argentophilicity interactions are weakened, and the hydrogen bonds are strengthened. Consequently, their water stabilities and photocurrents are improved, in which the Ag-4d/Br-4p to π* anti-bonding orbital of the quaternary phosphorus transfer is facilitated. Furthermore, the greenish blue emissions can be detected. Finally, high inhabitation rates against Streptococcus mutans and Candida albicans can be observed in 2 and 3. CONCLUSION: In all experiments, by elongating the spacer lengths of quaternary phosphorus salts, multifunctions were integrated in the quaternary phosphorus/bromoargentate hybrids, including greenish blue luminescence, repeatable photocurrent responses and durable antimicrobial activities with enhanced water stability. This work could provide a theoretical guide for the design of new biologically multifunctional materials.