morin and Mouth-Neoplasms

Toxic components of STE induced serious, adverse human oral health outcomes. In the present study, we observed that STE was involved in oral toxicity by reducing the viability of human squamous epithelial cells, SCC-25, along with the simultaneous induction of both apoptosis and autophagic signaling. STE was also found to induce significant amount ROS generation in SCC-25 cells. The dietary flavonoid morin, found abundantly in a variety of herbs, fruits and wine, has been reported to attenuate ROS-induced pathogenesis including autophagy. In this study we designed three different treatment regimes of morin treatment, such as pre, co, and post - treatment of STE challenged SCC-25 cells. In all cases morin provided cytoprotection to STE challenged SCC-25 cells by augmenting STE induced ROS-dependent cytotoxic autophagy. Hence, morin is a potential option for antioxidant therapy in treatment of STE induced toxicity.

Topics: Carcinoma; Cell Line, Tumor; Epithelial Cells; Flavonoids; Humans; Molecular Structure; Mouth Neoplasms; Tobacco, Smokeless

Various naturally occurring flavonoids have been found to be cancer-protective in chemically induced animal cancer models and synthetic flavonoid derivatives are being tested for potential chemotherapeutic usefulness in clinical trials. This report demonstrates that human oral squamous carcinoma cells (SCC) are significantly more sensitive to growth inhibition by the naturally occurring flavonoid, morin (3,5,7,2',4'-pentahydroxyflavone) than normal oral mucosa (NOMC) (SCC IC(50) = 115 microM; NOMC IC(50) = 173 micro M; P for difference = 0.009). Structure/function comparisons indicate that both the 2' and 4' hydroxyl groups in morin are required for its tumour selectivity. Morin causes growth arrest in G(2)/M, without inducing apoptosis, and this is associated with induction of GADD45 and phosphorylation and inactivation of the cell cycle kinase, cdc2. Morin also has pleiotropic effects on kinase signalling pathways, including inhibition of activation of protein kinase B by mitogens (but not extracellular-regulated kinases 1/2) and activation of the stress pathway kinases, Jun N-terminal kinase and p38 kinase. p38 kinase activation is functionally important since inhibition of its activation by the specific inhibitor SB202190 partially prevented cell cycle arrest by morin. However, analysis of dose-response relationships reveals that the enhanced tumour sensitivity to morin may be explained by the fact that activation of AKT is inhibited at lower concentrations of morin in carcinomas than normal oral mucosa, whereas Jun N-terminal kinase, p38 kinase and GADD45 are all induced in parallel with the same dose-response curves in carcinomas and normal oral mucosa.

Topics: 3T3 Cells; Animals; Blotting, Western; Cell Division; CHO Cells; Cricetinae; Enzyme Activation; Flavonoids; Humans; JNK Mitogen-Activated Protein Kinases; Mice; Mitogen-Activated Protein Kinases; Mouth Neoplasms; p38 Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction; Structure-Activity Relationship; Tumor Cells, Cultured