scholarly journals Unfolding the Apoptotic Mechanism of Antioxidant Enriched-Leaves of Tabebuia pallida in EAC Cells

2021 ◽  
Author(s):  
Md. Mahbubur Rahman ◽  
Muhammad Ali Khan ◽  
A. S. M. Ali Reza ◽  
Khaled Mahmud Sujon ◽  
Rokshana Sharmin ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Caspase 3 ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition ◽  
Esi Ms ◽  
Apoptotic Genes ◽  
Parp 1 ◽  
Tabebuia Pallida ◽  
Eac Cells

AbstractTargeting apoptosis is a promising approach to inhibit the abnormal cell proliferation of cancer progression. Existing anti-apoptotic drugs, many derived from chemical substances, have often failed to combat cancer development and progression. Therefore, identification of apoptosis-inducing anticancer agents from plant-derived sources has become a key aim in cancer research. The present study was designed to explore the regulation of apoptosis by Tabebuia pallida (T. pallida) using an Ehrlich Ascites Carcinoma (EAC) mouse model and compositional analysis by LC-ESI-MS/MS. Dried and powdered T. pallida leaves (TPL), stem bark (TPSB), root bark (TPRB) and flowers (TPF) were extracted with 80% methanol. Using cultured EAC cells and EAC-bearing mice with and without these extracts, anticancer activities were studied by assessing cytotoxicity and tumor cell growth inhibition, changes in life span of mice, and hematological and biochemical parameters. Apoptosis was analyzed by microscopy and expression of selected apoptosis-related genes (Bcl-2, Bcl-xL, NFκ-B, PARP-1, p53, Bax, caspase-3 and -8) using RT-PCR. LC-ESI-MS analysis was performed to identify the major compounds from the most active extracts. In EAC mice compared with untreated controls, the TPL extract exhibited the highest cytotoxicity with significant tumor cell growth inhibition (p< 0.001), reduced ascites by body weight (p< 0.01), increased the life span (p<0.001), normalized blood parameters (RBC/WBC counts), and increased the levels of superoxide dismutase and catalase. TPL-treated EAC cells showed apoptotic characteristics of membrane blebbing, chromatin condensation and nuclear fragmentation, and caspase-3 activation, compared with untreated EAC cells. Moreover, annexin V-FITC and propidium iodide signals were greatly enhanced in response to TPL treatment, indicating apoptosis induction. Pro- and anti-apoptotic signaling after TPL treatment demonstrated up-regulated p53, Bax and PARP-1, and down-regulated NFκ-B, Bcl-2 and Bcl-xL expression, suggesting that TPL shifts the balance of pro- and anti-apoptotic genes towards cell death. LC-ESI-MS data of TPL showed a mixture of glycosides, lapachol, and quercetin antioxidant and its derivatives that were significantly linked to cancer cell targets. In conclusion, the TPL extract of T. pallida possesses significant anticancer activity. The tumor suppressive mechanism is due to apoptosis induced by activation of antioxidant enzymes and caspases and mediated by a change in the balance of pro- and anti-apoptotic genes that promotes cell death.Graphical Abstract

scholarly journals Anticancer effects of mifepristone on human uveal melanoma cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Prisca Bustamante Alvarez ◽  
Alexander Laskaris ◽  
Alicia A. Goyeneche ◽  
Yunxi Chen ◽  
Carlos M. Telleria ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Progesterone Receptor ◽  
Dna Fragmentation ◽  
Cell Lines ◽  
Caspase 3 ◽  
Annexin V ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Free Dna

Abstract Background Uveal melanoma (UM), the most prevalent intraocular tumor in adults, is a highly metastatic and drug resistant lesion. Recent studies have demonstrated cytotoxic and anti-metastatic effects of the antiprogestin and antiglucocorticoid mifepristone (MF) in vitro and in clinical trials involving meningioma, colon, breast, and ovarian cancers. Drug repurposing is a cost-effective approach to bring approved drugs with good safety profiles to the clinic. This current study assessed the cytotoxic effects of MF in human UM cell lines of different genetic backgrounds. Methods The effects of incremental concentrations of MF (0, 5, 10, 20, or 40 μM) on a panel of human UM primary (MEL270, 92.1, MP41, and MP46) and metastatic (OMM2.5) cells were evaluated. Cells were incubated with MF for up to 72 h before subsequent assays were conducted. Cellular functionality and viability were assessed by Cell Counting Kit-8, trypan blue exclusion assay, and quantitative label-free IncuCyte live-cell analysis. Cell death was analyzed by binding of Annexin V-FITC and/or PI, caspase-3/7 activity, and DNA fragmentation. Additionally, the release of cell-free DNA was assessed by droplet digital PCR, while the expression of progesterone and glucocorticoid receptors was determined by quantitative real-time reverse transcriptase PCR. Results MF treatment reduced cellular proliferation and viability of all UM cell lines studied in a concentration-dependent manner. A reduction in cell growth was observed at lower concentrations of MF, with evidence of cell death at higher concentrations. A significant increase in Annexin V-FITC and PI double positive cells, caspase-3/7 activity, DNA fragmentation, and cell-free DNA release suggests potent cytotoxicity of MF. None of the tested human UM cells expressed the classical progesterone receptor in the absence or presence of MF treatment, suggesting a mechanism independent of the modulation of the cognate nuclear progesterone receptor. In turn, all cells expressed non-classical progesterone receptors and the glucocorticoid receptor. Conclusion This study demonstrates that MF impedes the proliferation of UM cells in a concentration-dependent manner. We report that MF treatment at lower concentrations results in cell growth arrest, while increasing the concentration leads to lethality. MF, which has a good safety profile, could be a reliable adjuvant of a repurposing therapy against UM.

Cranberry Phenolics: Effects on Oxidative Processes, Neuron Cell Death, and Tumor Cell Growth

2005 ◽  
pp. 271-282 ◽  
Author(s):  
Catherine C. Neto ◽  
Marva I. Sweeney-Nixon ◽  
Toni L. Lamoureaux ◽  
Frankie Solomon ◽  
Miwako Kondo ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Oxidative Processes

scholarly journals Caspase 3 Promotes Surviving Melanoma Tumor Cell Growth after Cytotoxic Therapy

2014 ◽  
Vol 134 (6) ◽  
pp. 1686-1692 ◽  
Author(s):  
Anne L. Donato ◽  
Qian Huang ◽  
Xinjian Liu ◽  
Fang Li ◽  
Mary A. Zimmerman ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Caspase 3 ◽  
Tumor Cell Growth ◽  
Cytotoxic Therapy ◽  
Melanoma Tumor

Synthesis, characterization and tumor cell growth inhibition of new trans platinum complexes with phosphane derivatives

Polyhedron ◽  
2011 ◽  
Vol 30 (10) ◽  
pp. 1646-1650 ◽  
Author(s):  
A.G. Quiroga ◽  
F.J. Ramos-Lima ◽  
A. Alvarez-Valdés ◽  
M. Font-Bardía ◽  
A. Bergamo ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Platinum Complexes ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition

Tumor Cell Growth Inhibition by Liposome-Encapsulated Aromatic Polyamidines

1990 ◽  
Vol 79 (8) ◽  
pp. 672-677 ◽  
Author(s):  
C. Nastruzzi ◽  
R. Gambari ◽  
E. Menegatti ◽  
P. Walde ◽  
P.L. Luisi
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition

scholarly journals Cytotoxicity and Antineoplastic Activities of Alkylamines and Their Borane Derivatives

1996 ◽  
Vol 3 (2) ◽  
pp. 101-112
Author(s):  
Iris H. Hall ◽  
Elaine Y. Tse ◽  
Rosallah A. Muhammad
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Ribonucleotide Reductase ◽  
Cultured Cells ◽  
Cytotoxic Action ◽  
Tumor Cell Growth ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Dna Template

The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition ribonucleotide reductase and nucleoside kinase activities were reduced by the agents which would account for the reduced d[NTP] pools. The DNA template or molecule may be a target of the drugs with regard to binding of the drug to nucleoside bases or intercalaction of the drug between DNA base pairs. Only some Of the agents caused DNA fragmentation with reduced DNA viscosity. These effects would contribute to overall cell death afforded by the agents.

scholarly journals In Vitro Tumor Cell Growth Inhibition Induced by Lophocereus marginatus (DC.) S. Arias and Terrazas Endophytic Fungi Extracts

2021 ◽  
Vol 18 (18) ◽  
pp. 9917
Author(s):  
Jesica M. Ramírez-Villalobos ◽  
César I. Romo-Sáenz ◽  
Karla S. Morán-Santibañez ◽  
Patricia Tamez-Guerra ◽  
Ramiro Quintanilla-Licea ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Endophytic Fungi ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition ◽  
Antitumor Effects ◽  
Ht 29 ◽  
Mcf 7

Endophytic fungi have become potential sources of antitumor agents, particularly against antineoplastic-resistant cancer cells, with marginal or nil adverse effects for the oncological patient. Endophytic fungi were isolated from stems of the Lophocereus marginatus cactus, commonly found in Mexico. Methanol extracts were then obtained from fungus liquid cultures and their effects on tumor cell growth against murine lymphoma (L5178Y-R), human colorectal adenocarcinoma (HT-29), and human breast cancer (MCF-7) cells were evaluated at concentrations ranging from 31 µg/mL to 250 µg/mL via the colorimetric 3- [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide reduction assay, using monkey kidney epithelial (MA-104) and human peripheral mononuclear (PBMC) cells as controls. Furthermore, we obtained the IC50 and the selectivity index (SI) was calculated from the IC50 ratio of normal and tumor cells. In addition, molecular identification of fungi showing cytotoxic activity was determined, using internal transcribed spacer molecular markers. PME-H001, PME-H002, PME-H005, PME-H007, and PME-H008 filamentous fungus strain extracts showed significant (p < 0.05) tumor cell growth inhibition. In particular, they significantly (p < 0.05) inhibited L5178Y-R cell growth, whereas the least susceptible cell line was HT-29. The endophytic strain PME-H008 of Cladosporium sp. caused the highest growth inhibition percentage against L5178Y-R and HT-29 cells with 96.6% (p < 0.01) and 42.5% (p < 0.05) respectively, and the highest SIs against L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMCs, respectively, whereas the PME-H005 extract showed SIs of 2.77 and 1.5 against MCF-7 and L5178Y-R cells, respectively, as compared with PBMCs. In addition, the endophytic strain PME-H007 of Metarhizium anisopliae caused the highest percentage of growth inhibition (p < 0.01) against MCF-7 cells with 55.8% at 250 µg/mL. We demonstrated in vitro antitumor effects of L. marginatus endophytic fungi. Further research will involve the isolation and in vivo testing of bioactive compounds.

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