The luminescent Chalcones. Its potential use as a luminescent and antitumoral agents / Chalconas luminiscentes. Su uso potencial como agentes luminiscentes y antitumorales

Background: Hepatocellular carcinoma (HCC) is one of the most diagnosed cancers worldwide. Chemoprevention of HCC can be achieved using natural or synthetic compounds that reverse, suppress, detect, or prevent cancer progression. Objectives: In this study, both the antiproliferative effects and luminescent properties of 2'-hydroxychalcones were evaluated. Methods: Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay, spectroscopy assays, and density functional theory (DFT) calculations were used to determine the luminescent properties of 2 ́-hydroxychalcones. Results: Cytotoxic effects of 2 ́-hydroxychalcones were observed over the HepG2 and EA.hy926 cells. Since the chalcone moiety could be used as a fluorescent probe, these compounds may be helpful in cancer diagnosis and tumor localization. They may enable tumor observation and regression through the fluorescence during treatment; therefore, the compounds are a potential candidate as novel anticancer agents acting on human hepatomas. Conclusions: This report describes the chalcones' use as a specific luminescent biomarker in tumor cells. We also report the cellular uptake of 2'-hydroxychalcones, their cellular distribution, and the mechanisms that may be responsible for their cytotoxic effects

ANTECEDENTES: El carcinoma hepatocelular (CHC) es uno de los cánceres más diagnosticados en todo el mundo. La quimio prevención del CHC se puede lograr utilizando compuestos naturales o sintéticos que reviertan, supriman, detecten o prevengan la progresión del cáncer. OBJETIVOS: En este estudio, se investigó tanto los efectos antiproliferativos como las propiedades luminiscentes de las 2'-hidroxicalconas. MÉTODOS: La viabilidad celular se evaluó usando el ensayo colorimétrico (MTT), los ensayos de espectroscopia y los cálculos DFT se usaron para determinar las propiedades luminiscentes de las 2 ́-hidroxichalconas. RESULTADOS: Se observaron efectos citotóxicos sobre las líneas celulares del tipo HepG2 y EA.hy926. Dado que la estructura de la 2 ́-hidroxichalcona puede ser usada como sonda fluorescente, estos compuestos pueden ser útiles en el diagnóstico del cáncer y la localización del tumor, ya que pueden permitir la observación a través de la fluorescencia y la regresión del tumor durante el tratamiento, por lo que son candidatas potenciales como nuevos agentes anticancerígenos que podrían actuar sobre hepatomas humanos. CONCLUSIONES: Este trabajo describe el uso de las 2 ́-hidroxichalconas como un biomarcador luminiscente específico para células tumorales. También informamos la captación celular de 2>-hidroxicalconas, su distribución celular y los mecanismos que pueden ser responsables de sus efectos citotóxicos

Chemical profiles and anticancer effects of saponin fractions of different polarity from the leaves of Panax notoginseng / 中国天然药物

AIM@#To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macroporous resin from the leaves of Panax notoginseng.@*METHOD@#The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MS(n) analysis. The cytotoxic effects were determined against KP4 cells (human pancreatic cancer), NCI-H727 cells (human lung cancer), HepG2 cells (human hepatocellular cancer), and SGC-7901 cells (human gastric adenocarcinoma).@*RESULTS@#Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20(R)-Rg3, 20(S)-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity.@*CONCLUSION@#From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies.

Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

Flunitrazepam (FNZ) é um sedativo benzodiazepínico prescrito para o tratamento da insônia em curto prazo. Entretanto, existe a preocupação com relação aos possíveis efeitos carcinogênicos ou genotóxicos causados por este fármaco. Então, o objetivo deste estudo foi avaliar os efeitos citotóxicos, clastogênicos e aneugênicos do FNZ em células de hepatoma de Rattus norvegicus (HTC) in vitro e em células de medula óssea de ratos Wistar in vivo. Foram testadas as concentrações de 0,2, 1,0 e 10 μg/mL de FNZ pelo teste do micronúcleo com bloqueio de citocinese in vitro e 7, 15 e 30 μg/mL/kg de peso corpóreo para o teste de aberração cromossômica in vivo. Os resultados mostraram que as concentrações do benzodiazepínico testadas não foram citotóxicas, aneugênicas ou clastogênicas. Entretanto, considerando os efeitos adversos do uso deste benzodiazepínico, mais estudos são necessários.

Synergistic Cytotoxic Effects of Zole-dronic Acid and Radiation in the MCF-7 Human Breast Cancer Cell Line / 한국유방암학회지

PURPOSE: The clinical use of the zoledronic acid has been increasing recently, and especially for the treatment of bone metastases. The synergistic effects of zoledronic acid with other chemotherapeutic agents have been shown. However it is not known whether a similar synergistic apoptotic effects exist for a combination therapy of zoledronic acid with radiation. METHODS: The MCF-7 human breast cancer cell lines were treated with 10 micrometer, 50 micrometer or 100 micrometer of zoledronic acid, irradiated with 5 Gy, and they were also treated with a combination of both treatments. The results of the synergistic effect on apoptosis were identified by performing XTT assay, DNA fragmentation assay, FACS analysis and western blot analysis at 24, 48, 72 hours after treatment. RESULTS: Zoledronic acid afftects anti-proliferative and apoptotic effects on MCF-7 breast cancer cell line in a dose-dependent manner. The synergistic cytotoxic effect of zoledronic acid and radiation was noted. The western blot analysis suggested that this synergistic effect has a relationship with the intracellular signal pathway especially with Ras, eventhough Bcl-2 and BAX expressions showed no difference in a zoledronic acid and combination treatment group compared to a control group significantly, CONCLUSION: The combined use of zoledronic acid and radiotherapy shows enhanced in vitro cytotoxicity for the MCF-7 human breast cancer cell line. And in vivo study is under way to elucidate the effect of this combination therapy.

The relationship between LPS-induced iNOS mRNA expression and macrophages cytotoxic function / 中国癌症杂志

Purpose:To study LPS induced iNOS mRNA expression and NO production by murine peritoneal macrophages, and their relationship with cytotoxic function of activated macrophages.Methods:LPS induced iNOS mRNA expression, production of NO and effects of activated macrophages on anti tumor were investigated separately by RT PCR, nitrate reductase method and 3HTdR incorporation.Results:LPS can upregulates iNOS mRNA expression in a dose dependent manner. L NIL(specific inhibitors of iNOS) pretreatment significantly reduced cytotoxic effect on the proliferation of HL 60 cells, but had little effect on the K562 tumor target cells on condition that NO production is sufficiently inhibited. Conclusions:LPS can effectively induce iNOS mRNA expression and NO production in murine peritoneal macrophages. NO is one of the important effector molecules in unspecific immunity of activated macrophages, but it plays different roles in cytotoxic effects of macrophages on different target tumor cells.