Top PDF Antitumor Activity of Py-lm Polyamides

Antitumor Activity of Py-lm Polyamides

Antitumor Activity of Py-lm Polyamides

Polyamide cytotoxicity is reduced by proteasomal inhibition and serum starvation. Inhibition of RNAP2 has been reported to induce apoptosis (4, 6, 36), and may contribute to polyamide cytotoxicity observed in LNCaP cells cultured with 1 (Fig. 3.3A). A previous study with trabectidin, a DNA minor groove alkylator that causes RPB1 degradation, showed the toxicity induced by the molecule can be reduced by cotreatment with the proteasome inhibitor MG132(36). To evaluate if polyamide-induced toxicity was also reducible by proteasomal inhibition we treated LNCaP cells with 2 in the presence and absence of MG132. We developed analog 2 specifically for this application because prolonged incubation with MG132 alone is cytotoxic, and conjugation of an aryl group to the γ -aminobutyric acid turn have been shown to improve cellular uptake and cytotoxicity of polyamides. Cell viability experiments showed that 2 induced cell death more rapidly than 1 without significant change to DNA binding (Fig. S3.2A-B). Cell culture experiments revealed coincubation with MG132 reduced cytotoxicity induced by 2 (Fig. 3.3B) and prevented degradation of RPB1 (Fig. 3.3C). Polyamide nuclear uptake was not affected by MG132 (Fig. S3.2C-D). In addition, cytotoxicity studies of cells treated with UV radiation and α–amanitin have shown increased cellular sensitivity to transcription inhibition upon S phase entry(6, 37). Similarly, 2 was less toxic to LNCaP cells arrested in G 1 /G 0 by serum starvation as compared to cells grown in normal media
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Synthesis and Biological Studies of DNA binding Cyclic Py Im Polyamides

Synthesis and Biological Studies of DNA binding Cyclic Py Im Polyamides

While this in vivo toxicity is consistent with the perturbation of AR-mediated transcription by 1, there has also been mounting evidence in support of two alternate mechanisms. Genome-wide mapping of RNA polymerase II (RNAP2) occupancy using ChIP- seq showed preferential perturbation by 1 at transcription start sites (TSS). Along with an observed decrease in RNAP2 large subunit RPB1 levels following polyamide treatment, this suggests that the tumor reduction effects may result from inhibition of RNAP2 activity. The pro- apoptotic activity of 1 in AR-negative DU145 cells supports an AR- independent mechanism. Cell cycle analysis revealed polyamide-induced S-phase accumulation caused by inhibition of replicative helicase and subsequent stalling of replication forks. Although it is unclear how each of these pathways contributes toward tumor toxicity, it has been shown that the antitumor activity of 1 is not a result of DNA damage.
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Biological Activity of Pyrrole-Imidazole Polyamides in vivo

Biological Activity of Pyrrole-Imidazole Polyamides in vivo

the promoter regions of enhancer and transcription factor binding elements within DNA sequences (Fig. 6.1B) (33). The binding of Py-Im PA compounds results in allosteric changes to the DNA helix that interferes with DNA-protein interactions and modifies gene expression (22). These compounds have multiple advantages for targeting gene transcription: they are cell permeable, localize to the nuclei, and recognize and bind to specific regions of the minor groove of double helical DNA with affinity similar to transcriptional factors, such as HIF (22). Previous studies show antitumor effects of Py-Im polyamides in xenografts (20, 26, 28, 30); however, the effects of Py-Im polyamide treatment on Multiple Myeloma models have not been examined. Herein we evaluate those effects using a Py-Im polyamide (HIF-PA) that is capable of displacing heterodimer from binding to its cognate DNA sequences and inhibiting hypoxia-mediated gene transcription including pro-angiogenic factors (33). The choice of compound is dictated by observed heightened expression of angiogenic factors, such as VEGF, increased angiogenesis within MM tumors, and a strong correlation of these characteristics with disease development and progression in the BM and poor patient prognosis (34-37). Currently used VEGF-targeting drugs, such as bevacizumab (Avastin) inhibit angiogenesis in MM tumors; however, only modest and transient anti-tumor effects were observed (38), calling into question the overall clinical effectiveness of using a mono-therapeutic strategy targeting angiogenesis to treat myeloma. One explanation for the underwhelming effects of bevacizumab could be explained by a concomitant increase of hypoxia resulting from the inhibition of angiogenesis (39). In this scenario, low pO 2 (a natural component of the BM niche) may
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Antioxidant, antimicrobial and antitumor activity of genus Opuntia Spp

Antioxidant, antimicrobial and antitumor activity of genus Opuntia Spp

Madrigal-Santillán et al. [17] realized a study with species from Opuntia spp genus, and the authors used DPPH radical scavenging activity to measure the antioxidant activity. Results showed that three varieties of prickly pear juice have an antioxidant potential that depends on the concentration and the best range capacity corresponded to the red-purple juice. In addition, the authors suggest that antioxidant capacity of the juice may be involved in the anticlastogenic effect.

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Selective antitumor activity of roscovitine in head and neck cancer

Selective antitumor activity of roscovitine in head and neck cancer

transcriptionally active in HPV+ cells (Figure 2B and 2C). Cancer cells are usually very sensitive to reactivation of wild-type p53 and respond to ectopic p53 by apoptosis or growth arrest. Importantly, restoration of p53 function in established tumors results in tumor regression [49–52]. Restoring p53 expression has been suggested as a good strategy to combat HPV+ cancer. Indeed, several studies have shown that p53 stabilization in HPV+ cervical carcinoma by silencing E6 or E6AP activates the tumor suppressor function of p53 and kills cancer cells. The combination of leptomycin B and actinomycin D reduced expression of E6 mRNA and induced apoptosis via p53 upregulation [53]. A chemical library screen identified two small molecules that suppress the growth of cervical carcinoma cells by inhibiting E6 [54]. In addition, a synthetic peptide that binds E6 and inhibits its activity has been identified [55]. The small molecule RITA [56] protected p53 from degradation and killed cervical cancer cells [57]. We found that roscovitine-induced p53 upregulation was not due to inhibition of HPV E6 (Figure 2D). We therefore suggested a model in which roscovitine selectively induces DNA damage in HPV-positive head and neck cancer cells only, which in turn, stabilizes and activates p53, finally inducing substantial HPV+ cell death (Figure 9). Our model may not completely cover all the effects of roscovitine on p53, however, since we observed induction of p53 after the treatment in the absence of DNA damage in HPV-negative cells SCC61 carrying mutant p53 (Figure 1B). However, HPV- UNC-7 cells that harbor wild type p53 were resistant to roscovitine treatment, as
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Antitumor activity of silver nanoparticles biosynthesized by micro algae

Antitumor activity of silver nanoparticles biosynthesized by micro algae

UV spectrum showed that peaks wavelength varying from 400-450 nm -1 indicated the synthesis of AgNPs. At the beginning of the reaction the band recorded low wavelength and the reaction was carried out hasty. After 48hrs of the reaction the band was at high wavelength due to aggregation of nanoparticles forming large size of nanoparticles that needed less energy and hence longer wavelength due to poly dispersion of the nanoparticles [14]. So the reaction rate is directly proportional to reaction time till 48hrs of synthesis because after 48hrs, the activity of AgNPs in the solution were stable for a period of 2 months [17].
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Evaluation of Indonesian selected macroalgae for their antitumor and cytoprotective activity

Evaluation of Indonesian selected macroalgae for their antitumor and cytoprotective activity

Despite such advantages of natural products and a proven track record of succeeding discoveries, most pharmaceutical companies have been discouraged from pursuing natural product- based drug discovery due to perceived disadvantages of the natural products. These include challenges in ensuring access and adequate supply of potential natural product resources. Indonesia tropical warm waters are well-known as a suitable place for the macroalgae growth. Hence, it is endowed with an abundance of macroalgae (Tarman et al., 2011). However, there remains little information regarding Indonesian macroalgae pharmaceutical properties. The present study was, therefore, to evaluate pharmaceutical properties of selected macroalgae from Indonesian coastal areas; Acanthophora spicifera (ASE), Acanthophora muscoides (AME), Sargassum polycystum (SPE), and Sargassum crassifolium (SCE) crude ethanol extracts. We discovered that only ASE and AME provided selective cytotoxic activity in the human cells. However, SPE and SCE shown effectivity in the reduction of nuclear DNA damage induced by UVB radiation in human cervical cancer (HeLa) cells.
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Safety and antitumor activity of recombinant soluble Apo2 ligand

Safety and antitumor activity of recombinant soluble Apo2 ligand

proteins; upon cleavage by specific proteases, they can form soluble homotrimeric molecules (23). Whereas sol- uble TNF has strong agonist activity (5), soluble FasL is a very weak agonist and can antagonize the function of membrane-associated FasL, which has potent apopto- sis-inducing activity (24). Apo2L is also expressed as a type 2 transmembrane protein (6, 25, 26), and its extra- cellular region forms a soluble molecule upon cleavage (25). A polyhistidine-tagged soluble form of human Apo2L (amino acids 114–281) was biologically active (6, 27). In contrast, a Flag epitope–tagged form of human Apo2L (amino acids 95–281) was poorly active and required oligomerization by anti-Flag antibody (7) for potent biological activity. Recent work describes a solu- ble Apo2L fusion protein (termed LZ-TRAIL) in which the extracellular region of the ligand (amino acids 95–281) is linked to an exogenous, modified leucine zip- per that drives trimerization; this molecule is mostly homotrimeric and has biological activity (28). Injection of the LZ-TRAIL fusion protein in mice did not reveal any toxicity, and the molecule exhibited significant anti- tumor activity (28).
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Synthesis and Determination of Antitumor Activity of Jacaranone and Synthetic Analogs

Synthesis and Determination of Antitumor Activity of Jacaranone and Synthetic Analogs

In 1976, Farnsworth et al . reported [1] that methanolic extracts from the plant Jacaranda caucana (Bignoniaceae) showed activity against P-388 lymphocytic leukemia. The compound responsible for this activity was a benzoquinoid (a quinol) named as jacaranone, 1. Since then, this phytoquinoid has been isolated from many species of flowering plants of the families Asteraceae (or Composi- tae) [2] and Bignoniaceae [3], both widely distributed in the tropical and sub- tropical areas of the world [4]. Jacaranone, 1, has also been isolated from plants of the Pentaphylacaceae family [5] and from the algae Delesseria sanguinea (De- lesseriaceae) [6].
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Syntheses and antitumor activity of some 1,2,4 - triazine derivatives

Syntheses and antitumor activity of some 1,2,4 - triazine derivatives

The cyotoxic and antitumor activities of the synthesized compounds 3-7 were tested against the HCT-116 cell line according to method of Mossman [15], Gandadevi and Muthumary [16]. The inhibitory activities against Human colon carcinoma (HCT-116) cell was detected by using different concentrations of the tested compounds ( 50, 25, 12,5, 6.25, 3.125 and 1.56 mg) and the viability cells (%) was determined by the colorimetric method. The drug doxorubicin was used as standard.

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Antitumor Activity of Methanolic Extract of Pisonia Aculeata Leaf

Antitumor Activity of Methanolic Extract of Pisonia Aculeata Leaf

cells/mouse on day ‘0’ and treatment with MPA started 24 h after inoculation, at the doses of 200 & 400 mg/kg/day orally. The control group was treated with same volume of 0.9% sodium chloride solution. All treatments were carried out for 9 days and observation was carried out for 45 days. The animals were subjected for the analysis of median survival time (MST) of DAL group (n=6) and changes in body weight. The antitumor efficacy of MPA (200 & 400 mg/kg/day p.o.) was compared with that of 5-Fluorouracil (20 mg/kg/day i.p. for 9 days). MST was noted with reference to control. Survival times of the treated group (T) were compared with those of the control groups (C) using the following calculation.
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 ANTITUMOR ACTIVITY OF BERBERINE AGAINST BREAST CANCER: A REVIEW

 ANTITUMOR ACTIVITY OF BERBERINE AGAINST BREAST CANCER: A REVIEW

In various cell culture studies on normal cells as well as cell lines of multiple tumors, the anticancer activity of berberine has been comprehensively observed. The results of these studies can be summarized in various unique characteristics including: First, the anticancer potentials of berberine are different in various cells. As an example, B16 cell line of murine tumor cells was more receptive for berberine therapy than U937 cells of human promonocytic 53 . In

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A More Detailed IS LM Story

A More Detailed IS LM Story

Textbooks tell a fairly short IS-LM story. This paper of- fers a more detailed IS-LM story. Based on a nearly un- changed IS-LM framework (so that model complexity re- mains low), the more detailed story covers the money mul- tiplier, quantitative easing and central bank interest rate tar- geting (increasing explanatory power). Comparable explan- atory power is usually only achieved by highly complex models, which, however, are beyond the scope of most un- dergraduates and the wider public.

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Synthesis and in vitro antitumor activity of new benzothiazole and benzoxazole derivatives

Synthesis and in vitro antitumor activity of new benzothiazole and benzoxazole derivatives

Formation of a hybride structure between benzene ring and five membered thiazole or oxazole ring resulted in the formation of benzothiazole or benzoxazole, respectively.[1] Benzothiazole and benzoxazole rings were found to possess different pharmacological activities such as anti ‐ viral, [2] anti ‐ bacterial, [3] anti ‐ microbial, [4] fungicidal [5] and antitumor [6-8] activities. Introducing aryl pharmacophore to benzothiazole and benzoxazole at position 2 exhibited a wide range of biological properties specially cytotoxic activity. [9,10] 2-phenylbenzothiazoles showed its antitumor activity by resembling the ATP antagonistic effects of the natural products. Moreover, they have tyrosine kinase inhibitory properties, [11] (Compounds I-IV) [12-14]. In this work, we synthesized new compounds containing benzothiazole and benzoxazole derivatives substituted at position 2 with phenyl ring containing substituted amino and/or carbonitrile derivatives aiming at forming compounds having potent antitumor activity against human adenocarcinoma cell line (MCF-7).
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Synthesis and antitumor activity in vitro of glioperazine C and its derivatives

Synthesis and antitumor activity in vitro of glioperazine C and its derivatives

In summary, we have synthesized glioperazine C and its derivatives and tested their antitumor activities against K562, Hep2 and HT-29 cell lines. The results show that glioperazine C has potent inhibitory activities against Hep2 cell line. The preliminary SAR study of these compounds led to the identification of a potent cytotoxic compound 2a. Further modification of other position on glioperazine C and some other derivatives are ongoing.

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Antioxidant and antitumor activity of dirhenium dicarboxylates in animals with Guerin carcinoma

Antioxidant and antitumor activity of dirhenium dicarboxylates in animals with Guerin carcinoma

The antioxidant and anticancer properties of dirhenium dicarboxylates of cis- and trans- configu ration with different organic ligands in a model of tumor growth (Guerin carcinoma) were studied. It was shown that compounds of different configu ration had similar antitumor effect, and dirhe nium (III) cis-dicarboxylates were charac- terized by higher antioxidant activity and degree of activation of erythrocyte superoxide dismutase (SOD) in comparison with trans-isomers. The de- pendence between the structure of dirhenium (III) dicarboxylates and their ability to activate eryth- rocyte SOD in the model of tumor growth was shown for the first time. The in vitro studies have shown that rhenium compounds of cis- and trans- configu ration interacted similarly with erythrocyte SOD, changing the protein secondary structure. In contrast to trans-dicarboxylate, for cis-dicar- boxylate the SOD-like activity was demonstrated to be on the first minutes of the xantine-oxidase reaction. The studied features of the interaction between rhenium compounds and SOD in vitro ex- plain only partly the activation of SOD in experi- ments in vivo. The attempt is made to explain the differen ces in the mechanisms of antioxidant ac- tivity of dirhenium cis- and trans-dicarboxylates.
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Antitumor activity of nivolumab on hemodialysis after renal allograft rejection

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection

Novel cancer immunotherapies targeting programmed- death-1 (PD-1) and its ligand (PD-L1) have demonstrated remarkable anti-cancer activity and survival benefit lead- ing to regulatory approvals in metastatic melanoma, non- small cell lung cancer, and renal cell carcinoma [1, 2]. Clinical trials of nivolumab (Opdivo™), an IgG4 subclass PD-1-inhibiting antibody, and other similar immune checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concur- rent immunosuppression. However, organ transplant re- cipients are a high-risk cohort for developing metastatic cancer as a result of suppressed immune surveillance [3].
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Potential antitumor activity of novel DODAC/PHO-S liposomes

Potential antitumor activity of novel DODAC/PHO-S liposomes

The morphological analysis of cells by SEM showed that melanoma murine B16F10 cells die after the activation of pro- apoptotic mechanisms. The changes in the plasma membrane during apoptosis are mainly of a biochemical nature, with no involvement of morphological changes except for the loss of microvilli and consequent cytoplasmic retraction, which was observed in cells treated with the liposomal formulation. These were the key features of apoptosis. The presence of the lipid aggregates adhered to the membrane of the B16F10 cells, as well as spread in the culture medium after 24 hours of exposure, which can promote the maintenance of cytotoxic activity. The results show that the electrostatic interaction between DODAC and PHO-S, DODAC and PHO-S, and cell membrane can maximize the antitumor effects mediated by PHO-S. Thus, the set of results obtained in vitro demonstrate that DODAC/ PHO-S liposomal formulation presents great potential for the treatment of melanoma and hepatocellular carcinoma.
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Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Since ME-T maximized the cutaneous delivery of paclitaxel and was safer than the moderate irritant Triton, the efficacy of this formulation against basal cell carcinoma cells was studied and compared to a drug solution in propylene glycol. Cell viability after treatment with the unloaded formulations at any of the concentrations used was at least 80% (Figure 6). Paclitaxel-loaded solution and ME-T led to significant reduc- tions in cell viability (P,0.05) compared to the unloaded formulations, suggesting that the stronger cytotoxicity of the loaded formulations derive from the presence of the drug and that incorporation in the ME did not hinder drug activity.
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Home Automation Using Py-Ardomotics

Home Automation Using Py-Ardomotics

Cloud-based home appliance monitoring and controlling System is design and implement a home gateway to collect metadata from home appliances and send to the cloud[r]

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