Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of...

Bioavailability of curcumin: problems and promises.

Asymmetric enamine catalysis.

Native wood celluloses can be converted to individual nanofibers 3–4 nm wide that are at least several microns in length, i.e. with aspect ratios >100, by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation and successive mild disintegration in water. Preparation methods and fundamental characteristics of TEMPO-oxidized cellulose nanofibers (TOCN) are reviewed in this paper. Significant amounts of C6 carboxylate groups are selectively formed on each cellulose microfibril surface by TEMPO-mediated oxidation without any changes to the original crystallinity (∼74%) or crystal width of wood celluloses. Electrostatic repulsion and/or osmotic effects working between anionically-charged cellulose microfibrils, the ζ-potentials of which are approximately −75 mV in water, cause the formation of completely individualized TOCN dispersed in water by gentle mechanical disintegration treatment of TEMPO-oxidized wood cellulose fibers. Self-standing TOCN films are transparent and flexible, with high tensile strengths of 200–300 MPa and elastic moduli of 6–7 GPa. Moreover, TOCN-coated poly(lactic acid) films have extremely low oxygen permeability. The new cellulose-based nanofibers formed by size reduction process of native cellulose fibers by TEMPO-mediated oxidation have potential application as environmentally friendly and new bio-based nanomaterials in high-tech fields.

TEMPO-oxidized cellulose nanofibers

Stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Research data show that more resistant stem cells than common cancer cells exist in cancer patients.To identify unrecognized differences between cancer stem cells and cancer cells might be able to develope effective classification,diagnose and treat ment for cancer.

Stem Cells,Cancer and Cancer Stem Cells

Small-molecule H-bond donors in asymmetric catalysis.

Chiral Amine-Catalyzed Asymmetric Baylis−Hillman Reaction: A Reliable Route to Highly Enantiomerically Enriched (α-Methylene-β-hydroxy)esters

Development of a stable nitroxyl radical class of catalysts, 2-azaadamantane N-oxyl (AZADO) and 1-Me-AZADO, for highly efficient oxidation of alcohols is described. AZADO and 1-Me-AZADO exhibit superior catalytic proficiency to TEMPO, converting various sterically hindered alcohols to the corresponding carbonyl compounds in excellent yields.

2-Azaadamantane N-Oxyl (AZADO) and 1-Me-AZADO: Highly Efficient Organocatalysts for Oxidation of Alcohols

Curcumin (diferuloylmethane) is a dietary phytochemical with low toxicity that exhibits growth-suppressive activity against a variety of cancer cells and possesses certain chemopreventive properties. Curcumin has already been the subject of several clinical trials for use as a treatment in human cancers. Synthetic chemical modifications of curcumin have been studied intensively in an attempt to find a molecule with similar but enhanced properties of curcumin. In this study, a series of novel curcumin analogues were synthesized and screened for anticancer activity. New analogues that exhibit growth-suppressive activity 30 times that of curcumin and other commonly used anticancer drugs were identified. Structurally, the new analogues are symmetrical 1,5-diarylpentadienone whose aromatic rings possess an alkoxy substitution at each of the positions 3 and 5. Analysis of the effects of the analogues on the expression of cancer-related genes usually affected by curcumin indicated that some induced the down-regulation of beta-catenin, Ki-ras, cyclin D1, c-Myc, and ErbB-2 at as low as one eighth the concentration at which curcumin normally has an effect. The analogues, however, exhibited neither harmful nor growth-suppressive effects on normal hepatocytes where oncogene products are not activated. They also exhibited no toxicities in vivo that they may provide effective alternative therapies for the prevention and treatment of some human cancers.

https://mct.aacrjournals.org/content/molcanther/5/10/2563.full.pdf

Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer

5-Fluoro-2-azaadamantane N-oxyl (5-F-AZADO) realizes a simple, organocatalytic aerobic alcohol oxidation system that has a wide scope under mild conditions at ambient pressure and temperature and is weakly acidic and halogen- and transition-metal-free. The oxoammonium nitrate (5-F-AZADO+NO3−) works as a bifunctional catalyst of 5-F-AZADO and NOx that enables the catalytic aerobic oxidation of alcohols by itself (a metal-salt-free system).

Highly efficient, organocatalytic aerobic alcohol oxidation.

Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown. Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH+/CD133+). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined. Our results observed that ALDH+/CD133+ colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model. Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer.

/pdf/targeting-colon-cancer-stem-cells-using-a-new-curcumin-4yw1t9tw3a.pdf

Yoshiharu Iwabuchi

Papers

Chiral Amine-Catalyzed Asymmetric Baylis−Hillman Reaction: A Reliable Route to Highly Enantiomerically Enriched (α-Methylene-β-hydroxy)esters

2-Azaadamantane N-Oxyl (AZADO) and 1-Me-AZADO: Highly Efficient Organocatalysts for Oxidation of Alcohols

Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer

Highly efficient, organocatalytic aerobic alcohol oxidation.

Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030