Involvement of mitophagy-mediated cell death in colon cancer cells by folate-appended methyl-β-cyclodextrin

In recent years, colorectal cancer has gained great attention among various types of cancers. We previously synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) as a novel autophagic antitumor agent. In this study, to further elucidate the impact of FA-M-β-CyD as an antitumor agent, we evaluated cytotoxic activity and the antiproliferative effect in colon cancer cells and colorectal cancer model mice, respectively. As a result, FA-M-β-CyD showed potent cytotoxic activity in HCT116 cells, a human colon cancer cell line, through folate receptor-α (FR-α)-mediated cellular uptake. In addition, FA-M-β-CyD elicited autophagosome formation and induced mitophagy in HCT116 cells. Importantly, FA-M-β-CyD drastically reduced the number of tumor polyps in colorectal cancer model mice induced by azoxymethane/dextran sodium sulfate after intravenous injections once a week for 4 weeks. These results suggest that FA-M-β-CyD has the antiproliferative effect in the colorectal cancer, due to the FR-α-mediated endocytosis and mitophagy induction.     

Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway?

Trichostatin A (TSA), originally developed as an antifungal agent, is one of potent histone deacetylase (HDAC) inhibitors, which are known to cause growth arrest and apoptosis induction of transformed cells, including urinary bladder, breast, prostate, ovary, and colon cancers. However, the effect of HDAC inhibitors on human non-small cell lung cancer cells is not clearly known yet. Herein, we demonstrated that treatment of TSA resulted in a significant decrease of the viability of H157 cells in a dose-dependent manner, which was revealed as apoptosis accompanying with nuclear fragmentation and an increase in sub-G0/G1 fraction. In addition, it induced the expression of Fas/FasL, which further triggered the activation of caspase-8. Catalytic activation of caspase-9 and decreased expression of anti-apoptotic Bcl-2 and Bcl-XL proteins were observed in TSA-treated cells. Catalytic activation of caspase-3 by TSA was further confirmed by cleavage of pro-caspase-3 and intracellular substrates, including poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, a characteristic phenomenon of mitochondrial dysfunction, including mitochondrial membrane potential transition and release of mitochondrial cytochrome c into the cytosol was apparent in TSA-treated cells. Taken together, our data indicate that inhibition of HDAC by TSA induces the apoptosis of H157 cells through signaling cascade of Fas/FasL-mediated extrinsic and mitochondria-mediated intrinsic caspases pathway.     

Elemental contents in Napoleon’s hair cut before and after his death: did Napoleon die of arsenic poisoning?

Whether or not Napoleon died of arsenic poisoning is an open question on which debate has been active since 1960. This work examined several of his hairs, cut at different times and in different places: two pieces cut the day after his death on the island of St. Helena (1821) and two pieces cut seven years earlier (1814) during his first exile on the island of Elba. INAA results show that all of the samples of Napoleons hair have an elevated arsenic concentration. These results disfavor the arsenic poisoning theory. Aside from arsenic, 18 other elements are reported, providing additional information for examining the arsenic poisoning theory.     

Study of direction of cyclization of malonodithioamides as a method of investigation of reactivity of α-diazothioacetamides

The reaction of malonothioamides with benzene-sulfonyl azide and 2-azido-3-ethylbenzthiazolium tetrafluoroborate gave amides of 2-diazothiomalonic acid, which underwent cyclization to a mixture of 5-N-R-amino-1,2,3-thiadiazole-4-carbothioamides and 5-amino-1,2,3-thiadiazole-4-N-R-carbothioamides. The ratio of the isomeric thiadiazoles formed in this reaction is the same as in the reactions of 2-diazo-2-cyanoacetamides, 5-amino-1,2,3-thiadiazole- and 5-mercapto-1,2,3-triazole-4-carboxamides with P₄S₁₀ and of 5-amino-1, 2,3-thiadiazole-4-carbonitriles with H₂S; it is characteristic of the influence of substituents on the reactivity of -diazothioacetamides. It was found that the cyclization of the diazo compounds is accelerated when electron-acceptor substituents are attached to the nitrogen atom of the carbothioamide group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1106–1112, August, 1992.     

Neuroprotective effect from stem bark extracts of Knema laurina against H2O2- and Aβ1–42-induced cell death in human SH-SY5Y cells

The stem bark extracts of Knema laurina inhibited the hydrogen peroxide (H₂O₂)- and aggregated amyloid β-peptide 1–42 length (Aβ_1–42)-induced cell death in differentiated SH-SY5Y cells. Exposure of 250 μM H₂O₂ or 20 μM Aβ_1–42 to the cells for 24 h reduced 50% of cell viability. Pretreatment of cells with ethyl acetate extract (EAE) or n-butanol extract (BE) at 300 μg/mL and then exposure to H₂O₂ protected the cells against the neurotoxic effects of H₂O₂. Besides, methanolic extract (ME) at 1 and 10 μg/mL exerted neuroprotective effect on Aβ_1–42-induced toxicity to the cells. These results showed that EAE, BE and ME exhibited neuroprotective activities against H₂O₂- and Aβ_1–42-induced cell death. Flavonoids (3–6) and β-sitosterol glucoside (8) were isolated from the EAE. Compound 1 was isolated from hexane extract, and compounds 2 and 7 were isolated from dichloromethane extract. All these observations provide the possible evidence for contribution in the neuroprotective effects.     

Synthesis of a Pair of Derivatives of N-Methylpyrrole Polyamide

A pair of derivatives of tetrameric N-methylpyrrole polyamide were synthesized in order to develop a new method for the study of interaction of the polyamide derivatives with DNA. Indole acetic acid and nicotinic acid were introduced to the polyamide in the synthesized compound, which showed an expected red shift in the UV spectrum. These compounds may function as a potential tool in the detection of the polyamide binding to DNA.     

Structure of Potassium of Undecatungstomononickelosilicate

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Analysis of Significance of Unite Examination of AFP and DNA Polymorphism of P3 Promoter of IGF-ⅡGene

The DNA of P3 promoter region of IGF-Ⅱ gene was obtained by means of PCR technique. The examination of DNA polymorphism by restriction endonuclease BstE Ⅱ and the examination of AFP by bioluminescence immunoassay technique were carried out. The results have a significant difference(P<0.005). But the positive rate of AFP is higher than that of DNA polymorphism. The experimental result shows that the change of the DNA polymorphism of IGF-Ⅱis not the only carcinogenic factor. The suggested unite examination is the best method for the diagnosis of the primary hepatocellular carcinoma.     

Kinetics of tautomerization of 1,3,4,7-tetramethylisoindole

The kinetics of transformation of 1,3,4,7-tetramethylisoindole(1)to 1,3,4,7-tetramethyl-1H-isoindole(2)in water or in deuterium oxide at various pH or pD at 25℃ were measuredspectrophotometricalty.The results indicated that the transformation of 1 to 2 could be promotedby acid and base.From the solvent isotope effects and the fact that the 1-position of isoindole nucleusis electron-rich,the mechanism of this transformation is suggested.     

Synthesis of Related Compounds of Carotenoid

类胡萝卜素是一类奇特的色素，由高等植物和微生物光化学合成，作为防止单线氧通过光敏反应产生危害的必要基团，类胡萝卜素最近受到了关注。类胡萝卜素联于富勒烯上，既可大大增加在可见光区域光诱导电子转移的有效吸收断面，又可抑制富勒烯敏化单线氧的危害能力。合成了类胡萝卜素的相关化合物，报道的某些反应条件先进且简洁。     

Analysis of Significance of Unite Examination of AFP and DNA Polymorphism of P3 Promoter of IGF- Ⅱ Gene

IntroductionTheinnatecharacterofthesolidcarcinomaistheresultthatcellgrowthgetsoutofcontrol.Itsbasicreasonconsistsintheabnormalityofthetumorgene .SomeonethinksthatthegeneofIGF Ⅱisoneofthecancergenesofthe primaryhepatocellularcarcino ma[1] ,andalsothinkstheoverexpressionofthegeneofIGF Ⅱtakesplaceintheearlierperiodofthepri maryhepatocellularcarcinoma ,whichmaybetheear lierdiagnosticnormofprimaryhepatocellularcarcino ma .ThefurtherresearcheshavedemonstratedthattheactivationofIGF Ⅱ genepromo…     

Peculiarities of dissociative ionization of alkylcyclopentadienyl nitrosyl π-complexes of nickel

The decomposition of alkylcyclopentadienyl nitrosyl -complexes of nickel, (C₅H₄R)(NO)Ni (R=H, Et,i-Pr, CH₂Ph), under the action of electron impact has been studied. The nature of the nitrosyl ligand has been shown to be the factor determining the main fragmentation pathway which involves the abstraction of an NO molecule. The effect of the nature of the ligand on the ability of the molecular ion (C₅H₄R)LNi⁺ (L=C₅H₄R, C₅H₅, C₃H₅, NO) to rearrange with hydrogen atom migration from one ligand to another has been considered. The structure of the alkyl group R determines a competing fragmentation pathway involving cleavage of the -C-C bond with respect to the cyclopentadienyl ring in the substituent.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1985–1988, November, 1993.     

2D NMR Investigation of Dynamic Equilibrium of Tautomers of Gossypol

Gossypol was obtained as an yellow platelike crystal with m.p. 210-214o . In CDCl3 there were three tautomers of gossypol: I aldehyde, II lactol,III ketal , in equilibrium .Their total H 1 NMR spectra were assigned by means of 1D and 2D NMR techniques including 1H-1H cosy , DEPT , HMQC (1H Detected Heteronuclear Multiple Quantum Coherence) and HMBC (1H Detected Heteronuclear Multiple Bond Connectivity) experiments . This paper first reported that we took use of the 2D NMR t…     

Analysis of Chemical Incredients of Angelica Sinnesis——Analysis of Non-Volatile Constituents of Roots

In the present investigation,the non-volatile constituents of Danguei (Tang-Kuei) roots of Gansu origin [Angelica sinensis (Oliv.) Diels] were analyzed and thirty seven organic constituin s were also identified,fifteen of which have not been recorded in literature before,including a new optically active compound named as Angelicide and an antibiotie,Brereldin A.By plasma emission spectrometry,thirteen minor elements were also detecled     

TPSR Studies of the Activation of

TPSR　Studies　of　the　Activation　of　...     

Dependence of the basic properties of meso-nitro-substituted derivatives of β-octaethylporphyrin on the nature of substituents

Spectrophotometric titration is used to study the basic properties of a series of porphyrins with a continuously increasing degree of macrocycle deformation resulting from the introduction of strong electron-withdrawing substituents: 2,3,7,8,12,13,17,18-octaethylporphyrin (I), 5-nitro-2,3,7,8,12,13,17,18-octaethylporphyrin (II), 5,15-dinitro-2,3,7,8,12,13,17,18-octaethylporphyrin (III), 5,10,15-trinitro-2,3,7,8,12,13,17,18-octaethylporphyrin (IV), and 5,10,15,20-tetranitro-2,3,7,8,12,13,17,18-octaethylporphyrin (V). It is found that the values of logK _b (total basicity constants) obtained for the investigated compounds consistently diminish with an increase in the number of meso-substituents: 11.85 (I) > 10.45 (II) > 10.31 (III) > 10.23 (IV) > 9.56 (V). It is shown that two opposing factors, the steric and electronic effects of the substituents, change the basic properties of the above series of compounds.