The synergistic effect exerted by the HDAC inhibitor SAHA and the sesquiterpene lactone parthenolide on triple negative breast canc er cells

Triple-negative breast cancer (TNBC) is a subtype o f breast cancer, insensitive to endocrine therapy. Chemotherapy is the main form of treatment, but is accompanied by a high rate of recidivism. The sesquiterpene lactone Parthenolide (PN) exerts a cy totoxic effect on MDA-MB231 cells, a TNBC cell line (1), but was ineffective at low doses (2-5μM). This repr esents an obstacle for a therapeutic utilization of PN. We supposed, in line with other authors (2), that PN c auses a protective response, which at low doses pre vails on the cytotoxic effect. With the aim of inhibiting this protective effect we have shown that pre-trea tment of MDA-MB231 cells with SAHA (2-5μM), an histone deace tylat…

Effetti benefici degli oli essenziali nel trattamento anti-obesità

Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors

PURPOSE:To examine the apoptotic effect induced in human retinoblastoma Y79 cells by camptothecin, etoposide, and amsacrine, to examine the effect of these drugs on the expression of many apoptosis-related modulators, and to test the antiapoptotic effect exerted by insulin-like growth factor-I (IGF-I). METHODS:Morphologic features of apoptosis were demonstrated using acridine orange- ethidium bromide staining and electron microscopy. DNA fragmentation was determined by means of an in situ cell detection procedure (TdT-dUTP terminal nick-end labeling [TUNEL]) or by electrophoresis on agarose gels and was quantified by enzyme-linked immunosorbent assay. The expression of apoptosis-related mod…

The apoptotic effects and synergistic interaction of sodium butyrate and MG132 in human retinoblastoma Y79 cells

This study deals with the apoptotic effect exerted on human retinoblastoma Y79 cells by both sodium butyrate and an inhibitor of 26S proteasome [z-Leu-Leu-Leu-CHO (MG132)] and their synergistic effect. Exposure to sodium butyrate (1-4 mM) induced an accumulation of cells in the G2-M phase that was already visible after 24 h of treatment, when morphological and biochemical signs of apoptosis appeared only in a small number of cells (5-10%). Thereafter, the apoptotic effects increased progressively with slow kinetics, reaching a maximum after 72 h of exposure, when they concerned a large fraction of cells (>75% with 4 mM sodium butyrate). Sodium butyrate stimulated the conversion of procaspas…

Increased cyclin E level in retinoblastoma cells during programmed cell death

The electrofunctional investigations in the diagnosis of orbital diseases

The importance of electrofunctional examinations (electroretinography, electro-oculography and visual evoked potentials) in orbital diseases is emphasized. Although such tests cannot give the same support to the clinical diagnosis as ultrasonography or CT scanning, they do give information about the functional state of the various orbital components. Visual evoked potentials can monitor the functionality of the optic nerve during and after trauma or compressive orbital diseases; electroretinography shows retinal changes secondary to traumatic or vascular orbital diseases, while electro-oculography allows to record extraocular muscle dysfunction.

Effects of retinotoxic drugs on rats heterozygotic for recessive retinitis pigmentosa

Methodological Aspects of the Application of the Naka-Rushton Equation to Clinical Electroretinogram

The nonlinear relation between stimulus intensity and response amplitude of the electroretinogram (ERG) scotopic b wave can be described by a curve based on the Naka-Rushton (NR) equation. Up to now, the NR equation has been used to assess the features of the normal and pathological ERG, but the best approach for a correct evaluation of the parameters is still debatable. The parameters are thought to be related to the different conditions of retinal activities. The method is well known in experimental laboratories but is quite unusual at the clinical level. In the present paper the derivative analysis of the NR function is proposed as an easier approach to understand the variations of the N…

Synthesized benzamido derivatives exert antiproliferative effects by DNA damage and ROS generation.

In this study we explored the effect and the biological action of synthesized benzamido derivatives bearing the (1S,2S)-2-phenyl-cyclopropane-1-carboxamido, 1,1'-biphen-2-carboxamido and 1,1'-biphen-4-carboxamido moieties on K562, a human leukemia cell line. Among the synthesized compounds a particular antiproliferative action was observed with the benzamido derivative bearing the 2-1,1'-biphenyl moiety with the substitution at the 5 position of the benzamido moiety with iodine. This compound showed cytotoxic effects in K562 leukemic cells at nanomolar concentrations and was, therefore, chosen as compound to explore its mode of action. Our analyses provided evidence that this benzamido deri…

Synthesis and antirpoliferative activity of isoxazolo[3,4-d]pyridazin-7(6H)-one derivatives

3,4-diphenylisoxazolo[3,4-d]pyridazin-7(6H)-one analogs were synthesized and tested for the antiproliferative activity. Study on the cell cycle alteration and on some cellular target (ATM, procaspase-2 proteins and H2AX histone) demonstrate the increase of the cell population in S phase and to induce cellular death by apoptosis by DNA damage with double strand breaks.

Different modulatory effect of the synthetic cannabinoid WIN55,212-2 on tumor cell migration.

MicroRNAs are small non-coding regulatory molecules exerting pleiotropic action in different biological processes such as proliferation, differentiation, apoptosis, migration and metastasis. Deregulation of miRNA expression has been observed in various cancers, and accumulating data suggest that miRNAs can display an oncogenic, antioncogenic or an ambiguous behavior in relationship to tumor environment. In a previous research we showed that the synthetic cannabinoid WIN55,212-2 is able to reduce the migratory activity of osteosarcoma MG63 cells analyzed by means of wound healing assay. So we undertook a study to evaluate the biochemical mechanism through which WIN plays this action. To this…

Ethanol promotes survival and tumor progression of colon cancer cells

In the Western Countries, colon cancer is the third tumor for aggressiveness and incidence after lung and breast/prostate cancer. Different risk factors concur to the development of colon cancer, including genetic factors, inflammation, intestinal microflora composition, as well as lifestyle. Epidemiologic studies correlating alcohol consumption and assert that the risks are 5-fold higher among drinkers compared to nondrinkers. However, the exact mechanisms correlating heavy alcohol drinking and colon cancer are not completely elucidated yet. To shed light on the biochemical mechanisms through which alcohol favors colon cancer progression, we evaluated the effect of high doses of ethanol (1…

Il sostegno e il miglioramento delle coltivazioni sub-tropicali in Sicilia traggono vantaggio dallo studio e dalla promozione delle loro proprietà nutrizionali.

Negli ultimi decenni si è assistito a un continuo progresso scientifico in ambito nutrizionale che ha trovato le sue basi da una parte nella scoperta dei principi nutritivi contenuti negli alimenti e dall'altra nell'elaborazione di precise linee guida a larga diffusione. Un'inadeguata alimentazione, infatti, oltre a incidere sul benessere psicofisico, rappresenta uno dei principali fattori di rischio per l'insorgenza di numerose patologie croniche. Secondo l'Organizzazione Mondiale della Sanità (OMS) il rischio di insorgenza di malattie cardiovascolari, metaboliche e di alcuni tumori si abbassa considerevolmente grazie a una corretta e sana alimentazione.

Retinal Sensibility to Drugs in Normal Rats and Carriers of Inherited Retinal Degeneration

Secondary retinitis pigmentosa of pseudo-retinitis pigmentosa can be brought about by certain diseases, especially exanthematic or viral ones.