Curcumin inhibits the growth via Wnt/ß-catenin pathway in non-small-cell lung cancer cells.

OBJECTIVE: In recent decades, the death rate from lung cancer appears to be an increasing yearly trend, particularly for non-small-cell lung cancer (NSCLC). Curcumin is a yellow pigment found in turmeric rhizomes, reported to exhibit various anti-inflammatory, anti-angiogenic, anti-proliferative, and antioxidant properties. Many reports have suggested that curcumin could induce apoptosis in malignant cells, and therefore, has great potential in tumor treatment. However, little is known about the effect of curcumin on NSCLC or its associated mode of action. Therefore, in this study, we explored curcumin's effect on NSCLC and investigated its associated mechanism. MATERIALS AND METHODS: The non-small-cell lung cancer (NSCLC) cell line A549 was cultured and subjected to MTT and clonogenic survival assays to assess cell proliferation. Reactive oxygen species (ROS) levels were measured using a Fluostar Omega Spectrofluorimeter. Superoxide dismutase (SOD) and γ-glutamyl cysteine synthetase (γ-GCS) activity in A549 cells were both determined by a commercial determination kit. Expression levels of p-GSK3ß (Ser9), c-Myc, cyclin D1, ß-catenin α-tubulin, and proliferating cell nuclear antigen (PCNA) were analyzed by Western blot. RESULTS: Results of the MTT and clonogenic survival assay indicated that curcumin reduced A549 proliferation. ROS levels and SOD and γ-GCS activities were detected. Curcumin decreased intracellular ROS levels and increased SOD and γ-GCS activity. Meanwhile, the ROS inhibitor N-Acetylcysteine (NAC) reversed the decrease in ROS levels and the increase in SOD and γ-GCS activity. These results indicate that oxidative stress is involved in the curcumin-induced reduction of A549 viability. Curcumin also strongly inhibited ß-catenin and p-GSK3ß (Ser9) protein expression, as well as the expression of downstream cyclin D1 and c-Myc. Similarly, NAC reversed the inhibition of ß-catenin and p-GSK3ß (Ser9) protein expression, as well as the expression of downstream cyclin D1 and c-Myc. CONCLUSIONS: We showed that curcumin inhibits NSCLC proliferation via the Wnt/ß-catenin pathway.

The effect of curcumin on cell adhesion of human esophageal cancer cell.

OBJECTIVE: Esophageal cancer is the 8th most common cancers worldwide and the 6th most common cause of death among cancers. Curcumin has been reported to have the function of anti-inflammatory, antioxidant, anti-rheumatoid, and anti-atherosclerosis role. It can also reduce lipid, eliminate free radicals and inhibit the growth of the tumor. Many reports had suggested that curcumin has shown great potential in the treatment of tumors by inducing apoptosis. Little is known about the effects of curcumin on cell adhesion of tumor cancer. Therefore, in this study, we attempted to look for a new approach to target resistant cells and improve efficacy without toxicity. MATERIALS AND METHODS: Human esophageal cancer cell line (Eca-109 cells) was cultured. Cell adhesion was detected under a microplate reader. Reactive oxygen species were measured using Fluostar Omega Spectrofluorimeter. SOD activity and GSH content in cells were detected by commercial determination kit. The expression of p-JAK, p-STAT3 and STAT3 were measured by Western blot and RT-PCR. RESULTS: Cell adhesion assay showed curcumin enhances cell-cell adhesion and cell-matrix adhesion in Eca-109 cells. ROS levels, SOD activity and total GSH content were detected and the results showed curcumin decreases intracellular ROS levels but increases SOD activity and total GSH content. Then, NAC (ROS inhibitor) and ICI (ER inhibitor) were pre-treated. Results showed ICI reversed the decreasing of intracellular ROS levels and the increasing of SOD activity and total GSH content affected by curcumin, but NAC had no such impact. Taken together, ER rather than ROS involves in cell adhesion affected by curcumin. Meanwhile, the downregulating of p-JAK, p-SATA3 and total STAT3 were caused by curcumin but NAC had no such influence. They were reversed by ICI, but NAC had no such influence. CONCLUSIONS: Curcumin could increase cell adhesion through inhibiting JAK/STAT3 mediated by ER in Eca-109.

Studies on the synthesis of myriaporones: stereoselective synthesis of the C5-C13 fragment starting from D-glucose via regioselective reductive opening of methoxybenzylidene acetal.

A stereoselective synthesis is described of the C5-C13 fragment (4) of myriaporone 4 (1) starting from D-glucose by a coupling of the C5-C9 aldehyde (5), prepared using a regioselective reductive ring-opening of methoxybenzylidene acetal, with the C10-C13 iodoolefin (6).

Synthetic studies of an 18-membered antitumor macrolide, tedanolide. 5. Stereoselective synthesis of the C13-C23 part via condensation of two fragments, C13-C17 and C18-C21, by taking advantage of the 3,4-dimethoxybenzyl protecting group.

An efficient and stereoselective synthesis of the C13-C23 part (8) was achieved starting from methyl (R)- and (S)-3-hydroxy-2-methylpropionates (9) via coupling of the C13-C17 aldehyde (6), prepared by Evans asymmetric aldol reaction, with the C18-C21 iodoalkene (5b) by taking advantage of the 3,4-dimethoxybenzyl protecting group.

Synthetic studies of the 18-membered antitumor macrolide, tedanolide. 3. Stereocontrolled synthesis of the C1-C12 part via a synthesis of the C1-C7 fragment by a mismatched but efficient sharpless dihydroxylation and its coupling with the C8-C11 fragment.

The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and the C8-C11 iodoalkene (7a). For a synthesis of 6, a mismatched but highly efficient Sharpless dihydroxylation of the alpha, beta-unsaturated ester (15) with AD-mix-alpha was successfully applied. Compound 7a was synthesized using hydrozirconation to the alkyne (32).