The colorimetric reversibility of polydiacetylene supramolecules, derived from a variety of functionalized diacetylenic lipids, has been subjected to detailed investigation. In an earlier effort, it was shown that polydiacetylene vesicles prepared from PCDA-mBzA 1, bearing terminal m-carboxyphenylamido groups, display complete reversibility upon thermal stimulation [J. Am. Chem. Soc. 2003, 125, 8976]. The origin and nature of reversible thermochromism in these systems have been elucidated insitu in the current studies by using polydiacetylene supramolecules, prepared from analogues of PCDA-mBzA 1. Issues related to the effects of (1) internal amide groups, (2) headgroup aromatic interactions, (3) lengths of the hydrophobic alkyl chains, and (4) terminal carboxylic groups on the colorimetric reversibility of the polydiacetylene supramolecules have been probed. The results demonstrate that welldeveloped hydrogen-bonding and aromatic interactions between headgroups are essential for complete recovery of the length of the conjugated π-electron chain following thermal stimulus. The results of this comprehensive investigation allow for the first time the rational design of reversible colorimetric sensors based on polydiacetylene supramolecules.

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Background3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both in vivo and in vitro models. We have previously determined that DIM (0 – 30 μmol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells.MethodsHT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and in vitro kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted.ResultsThe percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1 and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1.ConclusionHere, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.

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The colorimetric stability upon thermal stress of a series of conjugated polymer supramolecules prepared from 10,12‐docosadiyndioic acid (DCDDA)‐derived diacetylene monomers has been explored. Polydiacetylenes obtained from DCDDA‐bis‐mBzA 3, containing m‐carboxyphenylanilido groups at the both ends of the monomer, were observed to be highly colorimetrically stable upon thermal stimulation. The blue color of a solution containing these polydiacetylene vesicles remains unchanged even when the vesicles were subjected to boiling water. The unusual colorimetric stability is further demonstrated by the observation that blue color persists until vesicles in ethylene glycol are heated to 140 °C. The nature of this unusual thermal stability was elucidated by using polydiacetylene supramolecules, prepared from analogs of DCDDA‐bis‐mBzA 3. The presence of internal amide groups as well as aromatic interactions was found to be essential for the high colorimetric stability of the polydiacetylene supramolecules.

Isoliquiritigenin (ISL), a flavonoid chalcone that is present in licorice, shallot, and bean sprouts, is known to have antitumorigenic activities. The present study examined whether ISL alters prostate cancer cell cycle progression. DU145 human and MatLyLu (MLL) rat prostate cancer cells were cultured with various concentrations of ISL. In both DU145 and MLL cells treated with ISL, the percentage of cells in the G1 phase increased, and the incorporation of [(3)H]thymidine decreased. ISL decreased the protein levels of cyclin D1, cyclin E, and cyclin-dependent kinase (CDK) 4, whereas cyclin A and CDK2 expressions were unaltered in cells treated with ISL. The expression of the CDK inhibitor p27(KIP1) was increased in cells treated with 20 micromol/L ISL. In addition, treatment of cells with 20 micromol/L ISL for 24 hours led to G2/M cell cycle arrest. Cell division control (CDC) 2 protein levels remained unchanged. The protein levels of phospho-CDC2 (Tyr15) and cyclin B1 were increased, and the CDC25C level was decreased by ISL dose-dependently. We demonstrate that ISL promotes cell cycle arrest in DU145 and MLL cells, thereby providing insights into the mechanisms underlying its antitumorigenic activities.

Doxorubicin (DOX) is an anthracycline antibiotic, and has been recognized as one of the most effective anti-neoplastic agents in cancer chemotherapy. However, its usefulness is limited by its profound cardiotoxicity. Licorice is one of the most frequently prescribed agents in traditional herbal medicine, and is also employed as a natural sweetening additive. In traditional Chinese medicine, licorice root is added to a variety of herbal preparations to detoxify the effects of the other herbs in the preparation. In the present study, we explored the possibility that Glycyrrhiza uralensis licorice may alleviate DOX-induced cardiotoxicity. The hexane/ethanol extract of Glycyrrhiza uralensis (HEGU), which lacks glycyrrhizin, was prepared because glycyrrhizin intake has previously been reported to induce hypertension. In an effort to determine whether HEGU ameliorates DOX-induced cytotoxicity in H9c2 rat cardiac myoblasts, the cells were pretreated with 0-15 mg/L HEGU, then treated with doxorubicin. The pretreatment of cells with HEGU resulted in a significant mitigation of DOX-induced reductions in cell numbers (34 +/- 7%) and increases in apoptosis (53 +/- 1%). The Western blot analysis of cell lysates showed that HEGU suppressed DOX-induced increases in the levels of p53, phospho-p53 (Ser 15), and Bax. In addition, HEGU induced an increase in the levels of Bcl-xL, regardless of DOX-treatment. HEGU inhibited the DOX-induced cleavage of caspases 9, 3, and 7, as well as DOX-induced poly(ADP-ribose) polymerase cleavage. Furthermore, HEGU caused reductions in the viable cell numbers of HT-29 human colon cancer cells (IC50 = 10.7 +/- 0.3 mg/L), MDA-MB-231 human breast cancer cells (IC50 = 7.5 +/- 0.1 mg/L), and DU145 human prostate cancer cells (IC50 = 4.7 +/- 0.5 mg/L). HEGU augmented DOX-induced reductions in the viability of DU145 cells (15 +/- 1%). These results indicate that HEGU may potentially be an effective agent for the alleviation of DOX-induced cardiotoxicity.