Photocatalytic Decarboxylative Coupling of Arylacetic Acids with Aromatic Aldehydes

An efficient protocol was proposed for the preparation of secondary alcohols in good to excellent yields via photoredox-catalyzed decarboxylative couplings between readily available arylacetic acids and a variety of less reactive (hetero)aromatic aldehydes. The formation of carbanion is the key intermediate in this reaction. Various substituted arylacetic acids and aldehydes were all compatible with this transformation under mild reaction conditions. Furthermore, the current protocol was successfully applied to the direct alcoholization of several drug acids

Oleanolic Acid Suppresses Aerobic Glycolysis in Cancer Cells by Switching Pyruvate Kinase Type M Isoforms

<div><p>Warburg effect, one of the hallmarks for cancer cells, is characterized by metabolic switch from mitochondrial oxidative phosphorylation to aerobic glycolysis. In recent years, increased expression level of pyruvate kinase M2 (PKM2) has been found to be the culprit of enhanced aerobic glycolysis in cancer cells. However, there is no agent inhibiting aerobic glycolysis by targeting PKM2. In this study, we found that Oleanolic acid (OA) induced a switch from PKM2 to PKM1, and consistently, abrogated Warburg effect in cancer cells. Suppression of aerobic glycolysis by OA is mediated by PKM2/PKM1 switch. Furthermore, mTOR signaling was found to be inactivated in OA-treated cancer cells, and mTOR inhibition is required for the effect of OA on PKM2/PKM1 switch. Decreased expression of c-Myc-dependent hnRNPA1 and hnRNPA1 was responsible for OA-induced switch between PKM isoforms. Collectively, we identified that OA is an antitumor compound that suppresses aerobic glycolysis in cancer cells and there is potential that PKM2 may be developed as an important target in aerobic glycolysis pathway for developing novel anticancer agents.</p></div

OA treatment affects the expression profile of PKM isoforms in cancer cells in a dose- and time-dependent manner.

<p>PKM1 and PKM2 expression level was evaluated by immunoblotting assays in PC-3 and MCF-7 cells treated with 10, 25, 50,100 µg/ml OA respectively for 12 hr (<b>A</b>) or 100 µg/ml OA for 0.5, 1, 2, 3, 6, 12 hr respectively (<b>B</b>). β-tubulin was used as endogenous references. (<b>C</b>) The PKM2 levels (Green) were in PC-3 and MCF-7 cells treated with 100 µg/ml OA for 12 hr respectively, as determined by immunfluorescent staining. The nuclei (Blue) were stained with DAPI. The merged pictures were shown in the bottom of the panel. The fluorescence intensity was quantified with ImageJ software. The ratio of each group to control was presented here. The bars represented the average values of 5 randomly selected experiments.</p

OA suppression of aerobic glycolysis contributes to its anti-tumor activity.

<p>(<b>A</b>) PC-3 cells was counted 12, 24, 36 and 48 hr after the treatment of OA (100 µg/ml) or/and MHY1485 (2 µM) using hemacytometry. The average values of three independent experiments were shown as Mean ± SD. **, P<0.01. The representative figure was shown for each group. (<b>B</b>) Cells were treated with OA (100 µg/ml) or/and MHY1485 (2 µM) for 10 days, the number of colonies of PC-3 cells were counted and analyzed using ImageJ software. The representative figure was shown for each group. (<b>C</b>) OA suppresses the activation of mTOR in cancer cells. This inhibitory effect on mTOR signaling, in turn, abrogated c-Myc/hnRNPA1/hnRNPA2-dependent PKM2 expression. Consequently, the aerobic glycolysis was inhibited in cancer cells treated with OA.</p

OA suppresses the aerobic glycolysis in cancer cells.

<p>Glucose consumption (<b>A</b>), lactic acid production (<b>B</b>) and oxygen consumption (<b>C</b>) were assessed in PC-3 and MCF-7 cells treated with 50 or 100 µg/ml OA for 6 or 12 hr respectively. The details of methodology have been described in the section of Materials and Methods. The ratio of each group to control was presented here. The bars showed the average values of three independent experiments (Mean ± SD). *, P<0.05; **, P<0.01.</p

PKM2 overexpression abolishes the effect of OA on aerobic glycolysis in cancer cells.

<p>(<b>A</b>) OA-treated PC-3 cells were transfected with pWZL Neo Myr Flag PKM2 (Flag-PKM2) or control vector (Flag-GFP). Immunoblot assays were performed to determine the expression of PKM2 protein. β-tubulin was used as endogenous references. Glucose consumption (<b>B</b>), lactic acid production (<b>C</b>) and oxygen consumption (<b>D</b>) were assessed in PC-3 cells treated with 100 µg/ml OA for 12 hr. The details of methodology was described in the section of Materials and Methods. The ratio of each group to control was presented here. The bars showed the average values of three independent experiments (Mean ± SD). *, P<0.05; **, P<0.01.</p

The switch from PKM2 to PKM1 by OA results from the decrease in Myc, hnRNPA1 and hnRNPA2 expression.

<p>(<b>A</b>) The expression of c-Myc, hnRNPA1 and hnRNPA2 was determined by immunoblot analysis in PC-3 and MCF-7 cells treated with 50 or 100 µg/ml OA for 6 or 12 hr respectively. (<b>B</b>) The expressionof c-Myc, hnRNPA1 and hnRNPA2 expression was determined by immunoblot analysis in PC-3 cells treated with OA (100 µg/ml) or/and MHY1485 (2 µM) respectively. (<b>C</b>) The level of c-Myc, hnRNPA1, hnRNPA2, PKM1 and PKM2 was determined by immunoblot assays in PC-3 cells treated with plasmids pMXs-hcMYC (Flag-cMyc) in the presence or absence of OA. β-tubulin was used as endogenous references.</p

Oleanolic Acid Induces Metabolic Adaptation in Cancer Cells by Activating the AMP-Activated Protein Kinase Pathway

Cancer cells are well-known to require a constant supply of protein, lipid, RNA, and DNA via altered metabolism for accelerated cell proliferation. Targeting metabolic pathways is, therefore, a promising therapeutic strategy for cancers. Oleanolic acid (OA) is widely distributed in dietary and medicinal plants and displays a selective cytotoxicity to cancer cells, primarily by inducing apoptosis and cell cycle arrest. This study investigated if OA inhibited growth of tumor cells by affecting their metabolism. OA was found to activate AMP-activated protein kinase (AMPK), the master regulator of metabolism, in prostate cancer cell line PC-3 and breast cancer cell line MCF-7. AMPK activation is required for the antitumor activity of OA on cancer cells. Lipogenesis, protein synthesis, and aerobic glycolysis were inhibited in cancer cells treated with OA, in an AMPK activation-dependent manner. The metabolic alteration was shown to mediate the tumor suppressor activity of OA on cancer cells. Collectively, this study provides evidence that OA, as a widely distributed nutritional component, is able to exert antitumor function by interfering in the metabolic pathway in cancer cells. This finding should encourage researchers to study if affecting cancer metabolism is a common mechanism by which nutritional compounds suppress cancers

Uncommon Pyrazoyl-Carboxyl Bifunctional Ligand-Based Microporous Lanthanide Systems: Sorption and Luminescent Sensing Properties

Seven new isostructural lanthanide metal–organic frameworks (Ln-MOFs), [Ln­(Hpzbc)₂(NO₃)]·H₂O (<b>1-Ln</b>, Ln = Nd³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Er³⁺, and Yb³⁺ ions, H₂pzbc = 3-(1<i>H</i>-pyrazol-3-yl) benzoic acid), with one-dimensional (1D) channels decorated by nitrate anions and pyrazoyl groups have been constructed. <b>1-Ln</b>, as revealed by structural analysis, represent uncommon microporous 3D Ln-pyrazoyl-carboxyl systems using pyrazoyl-carboxyl bifunctional ligands as bridges. The luminescent investigations show that <b>1-Eu</b> is an excellent MOF-based fluorescent probe, with high sensitivity, selectivity, and simple regeneration, for environmentally relevant Fe³⁺ and Cr₂O₇^2– ions. <b>1-Eu</b> also presents highly selective capture for CO₂ over N₂ and CH₄ due to the multiple binding sites for CO₂ molecules, which were supported by Grand Canonical Monte Carlo (GCMC) simulations

Uncommon Pyrazoyl-Carboxyl Bifunctional Ligand-Based Microporous Lanthanide Systems: Sorption and Luminescent Sensing Properties

Seven new isostructural lanthanide metal–organic frameworks (Ln-MOFs), [Ln­(Hpzbc)₂(NO₃)]·H₂O (<b>1-Ln</b>, Ln = Nd³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Er³⁺, and Yb³⁺ ions, H₂pzbc = 3-(1<i>H</i>-pyrazol-3-yl) benzoic acid), with one-dimensional (1D) channels decorated by nitrate anions and pyrazoyl groups have been constructed. <b>1-Ln</b>, as revealed by structural analysis, represent uncommon microporous 3D Ln-pyrazoyl-carboxyl systems using pyrazoyl-carboxyl bifunctional ligands as bridges. The luminescent investigations show that <b>1-Eu</b> is an excellent MOF-based fluorescent probe, with high sensitivity, selectivity, and simple regeneration, for environmentally relevant Fe³⁺ and Cr₂O₇^2– ions. <b>1-Eu</b> also presents highly selective capture for CO₂ over N₂ and CH₄ due to the multiple binding sites for CO₂ molecules, which were supported by Grand Canonical Monte Carlo (GCMC) simulations