scholarly journals Toxicity and Anticancer Potential of Karwinskia: A Review

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5590
Author(s):  
Gilberto Jaramillo-Rangel ◽  
María-de-Lourdes Chávez-Briones ◽  
Alberto Niderhauser-García ◽  
Marta Ortega-Martínez
Keyword(s):  
Topoisomerase Ii ◽  
Human Cancer ◽  
Cell Types ◽  
Malignant Cell ◽  
Pathophysiological Mechanism ◽  
Selective Toxicity ◽  
Irreversible Damage ◽  
Human Cancer Cells ◽  
Antineoplastic Effect

Karwinskia genus consists of shrubs and small trees. Four toxic compounds have been isolated from Karwinskia plants, which were typified as dimeric anthracenones and named T496, T514, T516, and T544. Moreover, several related compounds have been isolated and characterized. Here we review the toxicity of the fruit of Karwinskia plants when ingested (accidentally or experimentally), as well as the toxicity of its isolated compounds. Additionally, we analyze the probable antineoplastic effect of T514. Toxins cause damage mainly to nervous system, liver, lung, and kidney. The pathophysiological mechanism has not been fully understood but includes metabolic and structural alterations that can lead cells to apoptosis or necrosis. T514 has shown selective toxicity in vitro against human cancer cells. T514 causes selective and irreversible damage to peroxisomes; for this reason, it was renamed peroxisomicine A1 (PA1). Since a significant number of malignant cell types contain fewer peroxisomes than normal cells, tumor cells would be more easily destroyed by PA1 than healthy cells. Inhibition of topoisomerase II has also been suggested to play a role in the effect of PA1 on malignant cells. More research is needed, but the evidence obtained so far indicates that PA1 could be an effective anticancer agent.

scholarly journals Endocrine Hormone Beta-estradiol and Anti-estrogen Letrozole Modulate 20:3 Isomer Production from 20:2n-6 in Human Cancer Cells (P08-119-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hui Gyu Park ◽  
Jae Hun Kim ◽  
Kumar S D Kothapalli ◽  
J Thomas Brenna
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Human Cancer ◽  
Methyl Esters ◽  
Cell Types ◽  
Mcf7 Cells ◽  
Human Cancer Cells ◽  
Flame Ionization ◽  
Funding Sources

Abstract Objectives The product of linoleic acid elongation, 20:2n-6, is the only known substrate for both FADS1 and FADS2. FADS1 catalyzes 20:2n-6 à 5Z,11Z,14Z-20:3 (sciadonic acid, SA), whereas FADS2 action yields 8Z,11Z,14Z-20:3 (DGLA). In certain cancer cell types, non-functional FADS2 activity unmasks 18:2n-6 elongation to 20:2n-6 and Δ5 desaturation by FADS1 to yield SA. Estrogen is known to inhibit Δ5-desaturation activity. Our objective was to examine the effect of 17-β-estradiol (estrogen) and the antiestrogen drug letrozole on the modulation of fatty acid desaturation and SA levels in vitro. Methods Estrogen doses (0 to 200 ppm) and letrozole doses (0 to 100 ppm) studies were performed using stably transformed MCF7 cells with either FADS1 or FADS2 or empty vector and five different (MCF7, HepG2, SK-N-SH, Y79 and Caco2) wild type cancer cells. Fatty acid methyl esters (FAME) were prepared from harvested cells and analyzed quantitatively by gas chromatograph-flame ionization detector (GC-FID). The peak structures were positively identified by GC-covalent adduct chemical ionization tandem mass spectrometry (GC-CACI-MS/MS). Results Increasing estrogen caused a decrease in the 5-desaturation product 5,11,14–20:3 in a dose-response manner in all cell types, but had no effect on DGLA. Letrozole exerted its effects most prominently in MCF7 cells. In response to increasing letrozole doses, DGLA increased, and SA decreased. Conclusions We provide the first biochemical evidence demonstrating letrozole enhancing FADS2-mediated DGLA levels in MCF7 cells. In all cell types estrogen reduced FADS1 mediated synthesis of SA. Both product fatty acids have anti-inflammatory activity, DGLA as a precursor to PGE1 and SA in displacing the largely proinflammatory arachidonic acid. Funding Sources NIH grant R01 AT007003.

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

Rhodium(i) N-heterocyclic carbene complexes: synthesis and cytotoxic properties

2021 ◽  
Vol 45 (11) ◽  
pp. 5176-5183
Author(s):  
Ichraf Slimani ◽  
Serap Şahin-Bölükbaşı ◽  
Mustafa Ulu ◽  
Enes Evren ◽  
Nevin Gürbüz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mtt Assay ◽  
Incubation Time ◽  
Human Cancer ◽  
Cytotoxic Activities ◽  
Carbene Complexes ◽  
Human Cancer Cells ◽  
Benzimidazolium Salts ◽  
Ht 29

A series of benzimidazolium salts and their [RhCl(NHC)(COD)] complexes were synthesized. All compounds were screened for in vitro cytotoxic activities against a panel of human cancer cells (HT-29 colon, Ishikawa endometrial, U-87 glioblastoma) using the MTT assay for 48 h incubation time.

scholarly journals Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protoporphyrin Ix ◽  
Cell Types ◽  
Amino Acid Derivative ◽  
Photodynamic Diagnosis

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

PLATELET ACTIVATION BY HUMAN CANCER CELLS GROWN “IN VITRO” OR DISSOCIATED FROM TUMOUR TISSUES

1987 ◽  
Author(s):  
G Grignani ◽  
L Pacchiarini ◽  
M Zucchella ◽  
L Dezza ◽  
S C Rizzo
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Human Cancer ◽  
Iodoacetic Acid ◽  
Tumour Cells ◽  
Human Cancer Cells ◽  
Human Tumour Cells ◽  
Dissociated Cells ◽  
Lymphoblastic Cells

The mechanisms of platelet activation by human tumour cells grown “in vitro” or freshly dissociated from tumour tissues have been investigated.MoCCL human T-lymphoblastic cells cultured “in vitro” induced platelet aggregation through the production of ADP, as evidenced by inhibition of the effect by apyrase. The maximum of ADP production by tumour cells was reached after 1 hour and was 225 p moles/106 cells.On the contrary, platelet aggregation induced by 5637 human bladder carcinoma cells was not inhibited by apyrase, but was abolished by hirudin, indicating the important role of thrombin in this effect.Tumour cells dissociated from 3 breast carcinomas showed a very high platelet aggregating activity, which was not inhibited by hirudin or apyrase, but was abolished by iodoacetic acid, suggesting a role for a cystein-protease in platelet activation.These results confirm that platelets can be activated by tumour cells through different mechanisms; they also suggest that the methods employed to obtain the tumour cells can influence the results, probably because of the different cell populations which are present in the dissociated tumour tissues.Informations obtained with freshly dissociated cells are interesting, because this method has been used seldom so far and because it provides a more physiological approach to the study of the interactions of tumours and platelets.

scholarly journals Study of the antiproliferative potential of seed extracts from Northeastern Brazilian plants

2011 ◽  
Vol 83 (3) ◽  
pp. 1045-1058 ◽  
Author(s):  
Paulo Michel P. Ferreira ◽  
Davi F. Farias ◽  
Martônio P. Viana ◽  
Terezinha M. Souza ◽  
Ilka M. Vasconcelos ◽  
...  
Keyword(s):  
Human Cancer ◽  
Ethanolic Extract ◽  
Cell Number ◽  
Northeastern Brazil ◽  
Human Cancer Cells ◽  
Ic50 Value ◽  
Underlying Mechanisms ◽  
Apoptotic Pathways ◽  
Seed Extracts

This study assessed the antiproliferative and cytotoxic potential against tumor lines of ethanolic seed extracts of 21 plant species belonging to different families from Northeastern Brazil. In addition, some underlying mechanisms involved in this cytotoxicity were also investigated. Among the 21 extracts tested, the MTT assay after 72 h of incubation demonstrated that only the ethanolic extract obtained from Myracrodruon urundeuva seeds (EEMUS), which has steroids, alkaloids and phenols, showed in vitro cytotoxic activity against human cancer cells, being 2-fold more active on leukemia HL-60 line [IC50 value of 12.5 (9.5-16.7) μg/mL] than on glioblastoma SF-295 [IC50 of 25.1 (17.3-36.3) μg/mL] and Sarcoma 180 cells [IC50 of 38.1 (33.5-43.4) μg/mL]. After 72h exposure, flow cytometric and morphological analyses of HL-60-treated cells showed that EEMUS caused decrease in cell number, volume and viability as well as internucleosomal DNA fragmentation in a dose-dependent way, suggesting that the EEMUS triggers apoptotic pathways of cell death.

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