scholarly journals Evaluating Medicinal Plants for Anticancer Activity

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Elisha Solowey ◽  
Michal Lichtenstein ◽  
Sarah Sallon ◽  
Helena Paavilainen ◽  
Elaine Solowey ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Plant Extracts ◽  
Human Cancer ◽  
Primary Cultures ◽  
Human Tumor ◽  
Modern Medicine ◽  
Breast Adenocarcinoma ◽  
Healthy Human ◽  
Whole Plant ◽  
Urtica Membranacea

Plants have been used for medical purposes since the beginning of human history and are the basis of modern medicine. Most chemotherapeutic drugs for cancer treatment are molecules identified and isolated from plants or their synthetic derivatives. Our hypothesis was that whole plant extracts selected according to ethnobotanical sources of historical use might contain multiple molecules with antitumor activities that could be very effective in killing human cancer cells. This study examined the effects of three whole plant extracts (ethanol extraction) on human tumor cells. The extracts were fromUrtica membranacea(Urticaceae),Artemesia monosperma(Asteraceae), andOriganum dayi post(Labiatae). All three plant extracts exhibited dose- and time-dependent killing capabilities in various human derived tumor cell lines and primary cultures established from patients’ biopsies. The killing activity was specific toward tumor cells, as the plant extracts had no effect on primary cultures of healthy human cells. Cell death caused by the whole plant extracts is via apoptosis. Plant extract 5 (Urtica membranacea) showed particularly strong anticancer capabilities since it inhibited actual tumor progression in a breast adenocarcinoma mouse model. Our results suggest that whole plant extracts are promising anticancer reagents.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

scholarly journals Antiproliferative activity of essential oils from three plants of the Brazilian Cerrado: Campomanesia adamantium (Myrtaceae), Protium ovatum (Burseraceae) and Cardiopetalum calophyllum (Annonaceae)

2020 ◽  
Vol 80 (2) ◽  
pp. 290-294 ◽  
Author(s):  
C. C. F. Alves ◽  
J. D. Oliveira ◽  
E. B. B. Estevam ◽  
M. N. Xavier ◽  
H. D. Nicolella ◽  
...  
Keyword(s):  
Essential Oils ◽  
Cell Line ◽  
Tumor Cells ◽  
Antiproliferative Activity ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Human Tumor ◽  
Lung Fibroblasts ◽  
Breast Adenocarcinoma ◽  
Brazilian Cerrado

Abstract Essential oils, which may be extracted from several parts of plants, have different biological activities. The Brazilian Cerrado has a large variety of plants that yield essential oils, even though many have not been studied yet. Taking into account the biodiversity of this biome, this study aimed at evaluating the antiproliferative activity of essential oils extracted from three species of plants of the Cerrado in Goiás state: Campomanesia adamantium (Cambess.) O. Berg, Protium ovatum (Engl. in Mart.) and Cardiopetalum calophyllum (Schltdl.). Essential oils were extracted from both C. adamantium and C. calophyllum leaves and from P. ovatum leaves and green fruits by hydrodistillation carried out by a Clevenger-type apparatus. The chemical composition of the essential oils was determined by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The following major chemical constituents were identified in the essential oils under investigation: β-myrcene (62.00%), spathulenol (28.78%), germacrene-B (18.27%), β-caryophyllene oxide (16.40%), β-caryophyllene (14.00%), α-pinene (11.30%), viridiflorol (9.99%), limonene (7.30%) and (Z,E)-pharnesol (6.51%). The antiproliferative activity was evaluated in different human tumor cell lines: breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) and glioblastoma (M059J). A normal human cell line was included (GM07492A, lung fibroblasts). Results showed that essential oils from C. adamantium leaves got the lowest values of IC50 in all strains of tumor cells under evaluation. They were significantly lower than the ones of the normal cell line, an evidence of selectivity. It is worth mentioning that this is the first report of the antiproliferative activity of essential oils from C. adamantium , P. ovatum and C. calophyllum against human tumor cells.

ARRY-649, a member of a novel class of Eg5 kinesin inhibitors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13045-13045 ◽  
Author(s):  
M. R. Miglarese ◽  
E. Wallace ◽  
R. Woessner ◽  
S. Allen ◽  
J. Hans ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Cancer ◽  
Intraperitoneal Administration ◽  
Xenograft Model ◽  
Human Tumor ◽  
Tumor Xenograft ◽  
Human Tumor Cells ◽  
Monopolar Spindle ◽  
Dividing Cells ◽  
Ht 29

13045 Background: Inhibitors of the Eg5 motor kinesin selectively disrupt mitotic spindles in dividing cells. This selective targeting of microtubule dynamics in dividing cells is expected to translate to broad-spectrum anti-tumor activity while avoiding neuropathic side effects caused by taxanes. To date, quinazolinone Eg5 inhibitors, exemplified by ispinesib, represent the only Eg5 inhibitors reported in clinical trials. Methods: We used X-ray crystallography, biochemical and cell-based assays, pharmacokinetic profiling and in vivo efficacy studies to identify and optimize a potent series of Eg5 inhibitors. Results: We have discovered a distinct series of potent Eg5 inhibitors, exemplified by ARRY-649. ARRY-649 inhibited Eg5 with an IC50 of 0.7 nM, blocked phosphorylation of histone H3 in HeLa cells with an IC50 of 0.3 nM and showed sub-nanomolar activity against a broad panel of human tumor cells lines in in vitro viability assays. Further evaluation of mechanism-of-action in tumor cell lines revealed that ARRY-649 induced a monopolar spindle phenotype and subsequent apoptosis characteristic of Eg5 inhibition. In contrast to paclitaxel, ARRY-649 retained potent activity against multi-drug resistant human tumor cells lines selected to overexpress P-glycoprotein. ARRY-649 demonstrated robust efficacy in the HT-29 human colon tumor xenograft model and was well-tolerated at efficacious doses and schedules. Durable complete- and partial-regressions were observed upon intraperitoneal administration on a 5 mg/kg q4dx3 schedule in the HT-29 model. Similar results were obtained using the HL-60 myelomonocytic xenograft model. Conclusions: ARRY-649 represents a distinct class of potent Eg5 inhibitors with robust activity in preclinical models of human cancer. Based on these observations, we have progressed novel Eg5 inhibitors toward clinical development. [Table: see text]

scholarly journals Simultaneous Detection of Different MicroRNA Types Using the ZIP-Code Array System

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Sonja U. Weishaupt ◽  
Steffen Rupp ◽  
Karin Lemuth
Keyword(s):  
Tumor Cells ◽  
High Throughput ◽  
Human Cancer ◽  
Simultaneous Detection ◽  
Human Tumor ◽  
Mirna Sequence ◽  
Single Experiment ◽  
Detection Range ◽  
Precursor Mirnas ◽  
Zip Code

MicroRNAs (miRNAs) are important negative regulators of gene expression. Their implication in tumorigenesis is based on their dysregulation in many human cancer diseases. Interestingly, in tumor cells, an altered ratio of precursor and mature miRNA levels has been described. Consequently, differences in miRNA type levels have a high potential as biomarkers and comparative high-throughput-based detection might permit a more accurate characterization of subtypes, especially in the case of very heterogeneous tumor entities. Several molecular methods exist for the detection of mature and precursor miRNAs. DNA microarrays are predestinated as a high-throughput method for comprehensive miRNA detection in tumors. However, the simultaneous array-based detection of both these miRNA types is limited because the mature miRNA sequence is identically present in both forms. Here we present a ZIP-code DNA microarray-based system in combination with a novel labeling approach, which enables the simultaneous detection of precursor and mature miRNAs in one single experiment. Using synthetic miRNA templates, we demonstrate the specificity of the method for the different miRNA types, as well as the detection range up to four orders of magnitude. Moreover, mature and precursor miRNAs were detected and validated in human tumor cells.

scholarly journals A Nonclonogenic Cytotoxicity Assay Using Primary Cultures of Patient Tumor Cells for Anticancer Drug Screening

1998 ◽  
Vol 3 (3) ◽  
pp. 207-216 ◽  
Author(s):  
Sumeer Dhar ◽  
Joachim Gullbo ◽  
Kenneth Nilsson ◽  
Peter Nygren ◽  
Rolf Larsson
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Anticancer Drug ◽  
Drug Screening ◽  
Primary Cultures ◽  
Human Tumor ◽  
Lymphocytic Leukemia ◽  
Cell Systems ◽  
Sensitivity Pattern

Primary cultures of cells from patients with chronic lymphocytic leukemia (CLL) and ovarian carcinoma (Ovca) were compared with the renal carcinoma ACHN and the lymphocytic CCRF-CEM human tumor cell lines in response to 63 toxic or nontoxic compounds. The experiments were conducted at 1, 10, and 100 μ/ml in 96-well microtiter plates for an assay time of 72 h. The plates were analyzed by the fully automated Dynatech Immuno Assay System (DIAS) using Alamar blue as a fluorometric/colorimetric indicator of metabolic activity. Drug response data were reported as the area under the tumor cell survival-concentration curve (AUC). Noncytotoxic compounds were classified as inactive by all cell systems. According to the AUC, CCRF-CEM and CLL cells were the most sensitive, followed by ACHN, and then Ovca. Many of the clinically active drugs were detected by all cell systems. However, the sensitivity pattern differed considerably between the cell types as judged from correlation analysis, and a higher proportion of clinically inactive drugs were scored as active by the cell lines compared with the primary cultures. Ovca showed the highest ratio of clinically solid tumor active/clinically inactive agents followed by CLL. The results indicate that primary cultures of human tumor cells may be a useful and valuable model for anticancer drug screening.

scholarly journals Copper(II) Complexes Containing Natural Flavonoid Pomiferin Show Considerable in Vitro Cytotoxicity and Anti-Inflammatory Effects

2021 ◽  
Vol 22 (14) ◽  
pp. 7626
Author(s):  
Ján Vančo ◽  
Zdeněk Trávníček ◽  
Jan Hošek ◽  
Tomáš Malina ◽  
Zdeněk Dvořák
Keyword(s):  
Ovarian Carcinoma ◽  
Human Cancer ◽  
Annexin V ◽  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Monocytic Leukemia ◽  
Healthy Human ◽  
Human Cancer Cell Lines ◽  
Anti Inflammatory

A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO3·2MeOH (1), [Cu(L)(dimebpy)]NO3·2H2O (2), [Cu(L)(phen)]NO3·2MeOH (3), [Cu(L)(bphen)]NO3·MeOH (4), [Cu(L)(dppz)]NO3·MeOH (5) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one, (pomiferin) and bpy = 2,2'-bipyridine, dimebpy = 4,4ʹ-dimethyl-2,2ʹ-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline, and dppz = dipyrido[3,2-a:2',3'-c]phenazine. The complexes were characterized using elemental analysis, infrared and UV/Vis spectroscopies, mass spectrometry, thermal analysis and conductivity measurements. The in vitro cytotoxicity, screened against eight human cancer cell lines (breast adenocarcinoma (MCF-7), osteosarcoma (HOS), lung adenocarcinoma (A549), prostate adenocarcinoma (PC-3), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1), revealed the complexes as effective antiproliferative agents, with the IC50 values of 2.2–13.0 μM for the best performing complexes 3 and 5. All the complexes 1–5 showed the best activity against the A2780R cells (IC50 = 2.2–6.6 μM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC50 > 100 μM. The complexes were evaluated by the Annexin V/propidium iodide apoptosis assay, induction of cell cycle modifications in A2780 cells, production of reactive oxygen species (ROS), perturbation of mitochondrial membrane potential, inhibition of apoptosis and inflammation-related signaling pathways (NF-κB/AP-1 activity, NF-κB translocation, TNF-α secretion), and tested for nuclease mimicking activity. The obtained results revealed the corresponding complexes to be effective antiproliferative and anti-inflammatory agents.

scholarly journals Adaptation of the Newcastle Disease Virus to Cell Cultures for Enhancing Its Oncolytic Properties

Acta Naturae ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 66-73
Author(s):  
K. S. Yurchenko ◽  
Yi. Jing ◽  
A. M. Shestopalov
Keyword(s):  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Disease Virus ◽  
Cell Cultures ◽  
Newcastle Disease ◽  
Human Cancer ◽  
Genetic Material ◽  
Human Tumor ◽  
Natural Strains

This study focuses on the adaptation of natural Newcastle disease virus (NDV) strains isolated from wild birds to human tumor cells. Many candidates for virotherapy are viruses pathogenic for human. During recombination of genetic material, there always exists a risk of getting a virus with an unstable genome. This problem can be solved by using natural apathogenic viruses as oncolytic agents. The Newcastle disease virus is the causative agent of contagious avian diseases. Its natural strains exhibit an antitumor effect and are considered safe for humans. As shown in earlier studies, the oncolytic properties of natural strains can be enhanced during adaptation to cell cultures, without interference in the virus genome. This study demonstrates that serial passaging increases the viral infectious titer in cancer cells. Moreover, the viability of tumor cells decreases post-infection when Newcastle disease virus strains are adapted to these cell cultures. The findings of this study complement the well-known data on the adaptation of the Newcastle disease virus to human cancer cells. Hence, it is possible to obtain a NDV strain with a more pronounced oncolytic potential during adaptation. This should be taken into account when choosing a strategy for designing anticancer drugs based on this virus.

Ceramide Glycanase Activities in Human Cancer Cells

1999 ◽  
Vol 19 (5) ◽  
pp. 449-460 ◽  
Author(s):  
Manju Basu ◽  
Patrick Kelly ◽  
Peter O'Donnell ◽  
Maria Miguel ◽  
Mathew Bradley ◽  
...  
Keyword(s):  
Double Bond ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Copper Ions ◽  
Human Cancer ◽  
Human Tumor ◽  
Supernatant Fraction ◽  
Enzyme Preparations ◽  
Human Cancer Cells ◽  
Ceramide Glycanase

Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 μM for nLcOse5[3H-DT]Cer and 350 μM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP, L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.

scholarly journals Antioxidant, Antiproliferative and Antimicrobial Activities of the Volatile Oil from the Wild Pepper Piper capense Used in Cameroon as a Culinary Spice

2013 ◽  
Vol 8 (12) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Verlaine Woguem ◽  
Filippo Maggi ◽  
Hervet P. D. Fogang ◽  
Léon A. Tapondjou ◽  
Hilaire M. Womeni ◽  
...  
Keyword(s):  
Essential Oil ◽  
Tumor Cells ◽  
Biological Activities ◽  
Human Tumor ◽  
Breast Adenocarcinoma ◽  
Moderate Activity ◽  
Oil Composition ◽  
Human Tumor Cells ◽  
Agar Disc

Wild pepper (Piper capense L.f., Piperaceae) is a spice traditionally used in western Cameroon to make soups called ‘ Nkui’ and ‘ Nah poh’. In the present work, the essential oil hydrodistilled from fruits was analyzed by GC-FID and GC-MS, and for in vitro biological activities, namely cytotoxic, antioxidant and antimicrobial, by MTT, DPPH, ABTS and agar disc diffusion methods. The oil composition was dominated by monoterpene hydrocarbons (56.5%) responsible for the pepper odor, such as β-pinene (33.2%), sabinene (10.0%) and α-pinene (8.9%). The oil induced a concentration-dependent inhibitory effect on human tumor cells MDA-MB 231 (breast adenocarcinoma), A375 (malignant melanoma) and HCT116 (colon carcinoma), showing IC50 values of 26.3, 76.0 and 22.7 μg/ml, respectively. The oil showed total antioxidant activity with a Trolox equivalent antioxidant concentration (TEAC) value of 140 μmol/g. The essential oil of P. capense proved to be an effective scavenger of the ABTS+ radical, with an activity only about 30 times lower than that of Trolox. Moderate activity was observed against the Gram-positive species Staphylococcos aureus and Enterococcus faecalis, and the yeast Candida albicans. The notable inhibition of some human tumor cells is worthy of further investigation to discover the possible mechanisms of action responsible for the observed cytotoxic effect of this essential oil.

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