Targeting apoptosis via inactivation of PI3K/Akt/mTOR signaling pathway involving NF-κB by geraniin in HT-29 human colorectal adenocarcinoma cells

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Chim Kei Chan ◽  
Liu Ying Tang ◽  
Bey Hing Goh ◽  
Habsah Abdul Kadir
Keyword(s):  
Colorectal Adenocarcinoma ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Morphological Changes ◽  
Biological Activities ◽  
Mtor Pathway ◽  
Human Cancer Cell Lines ◽  
Adenocarcinoma Cells ◽  
Underlying Mechanisms ◽  
Ht 29

Dietary phytochemicals possess a variety of biological activities which can be widely discovered in fruits, vegetables and herbs. Geraniin, an ellagitannin is commonly found in fruits and herbs which possesses multitude of health benefits including anti-diabetic, hepatoprotective, anti-inflammatory and anticancer. However, the effects of geraniin on human colorectal adenocarcinoma cells have yet to be evaluated. This study aimed to investigate the apoptotic effects of geraniin against selected human cancer cell lines and elucidate its underlying mechanisms. Geraniin exhibited the strongest cytotoxic effect on HT-29 cells as determined by MTT assay. Events of apoptosis induced by geraniin in HT-29 cells was portrayed by apoptotic morphological changes, externalization of phosphatidylserine, DNA fragmentation and dissipation of mitochondrial membrane potential. Western blot analysis was then used to investigate the mechanisms underlying observed growth inhibition. Geraniin was found to initiate p53 activation further resulting in elevation of Bak/Bcl-xL ratio and caspase-3 activation. This eventually led to HT-29 cell death via apoptosis. Additionally, exposure of geraniin on HT-29 cells found to suppress the PI3K/Akt/mTOR pathway and suppression of NF-kB. Cumulative evidences in this study suggests that geraniin inhibited colorectal adenocarcinoma cell proliferation via apoptosis induction and suppression of PI3K/Akt/mTOR pathway. Thus, these findings provide novel mechanistic insight for the therapeutic potential of geraniin in the treatment of colorectal adenocarcinoma.

scholarly journals Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents Through ROS-Mediated Apoptotic Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 207 ◽  
Author(s):  
Kuo Xu ◽  
Chuanlong Guo ◽  
Dayong Shi ◽  
Jie Meng ◽  
Haiying Tian ◽  
...  
Keyword(s):  
Human Cancer ◽  
Morphological Changes ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Apoptotic Pathway ◽  
Human Cancer Cell Lines ◽  
Planar Structures ◽  
Diphenyl Tetrazolium Bromide ◽  
Aspergillus Sp ◽  
Induced Apoptosis

A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (2−18). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.

scholarly journals Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

2021 ◽  
Vol 22 (11) ◽  
pp. 5482
Author(s):  
Zuo-Peng Zhang ◽  
Ye Zhong ◽  
Zhen-Bin Han ◽  
Lin Zhou ◽  
Hua-Sheng Su ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Human Cancer ◽  
Carbonic Anhydrases ◽  
Inhibitory Effects ◽  
Docking Analysis ◽  
Human Cancer Cell Lines ◽  
Hypoxic Conditions ◽  
Ca Ix ◽  
Topological Polar Surface Area ◽  
Ht 29

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

scholarly journals Aqueous Fraction of Nephelium ramboutan-ake Rind Induces Mitochondrial-Mediated Apoptosis in HT-29 Human Colorectal Adenocarcinoma Cells

Molecules ◽  
2012 ◽  
Vol 17 (6) ◽  
pp. 6633-6657 ◽  
Author(s):  
Chim Kei Chan ◽  
Bey Hing Goh ◽  
Muhamad Noor Alfarizal Kamarudin ◽  
Habsah Abdul Kadir
Keyword(s):  
Colorectal Adenocarcinoma ◽  
Aqueous Fraction ◽  
Adenocarcinoma Cells ◽  
Ht 29

Study on the Toxicity of Calix[4]- and [6]-Arenes and their Sulfated Derivatives in Two- and Three-Dimensional Cell Cultures of Colorectal Adenocarcinoma

2021 ◽  
Vol 37 (1) ◽  
pp. 87-94
Author(s):  
S.V. Nikulin ◽  
B.Ya. Alekseev ◽  
A.N Gorbunov ◽  
I.M. Vatsuro ◽  
V.V. Kovalev ◽  
...  
Keyword(s):  
Cell Culture ◽  
Colorectal Adenocarcinoma ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Russian Science ◽  
Adenocarcinoma Cells ◽  
Therapeutic Molecules ◽  
Derivatives Of ◽  
Ht 29 ◽  
Dimensional Cell

A comparative study of the toxicity of two unsubstituted calixarenes consisting of 4 and 6 phenolic fragments, as well as their p-sulfated derivatives, was carried out on the HT-29 colorectal adenocarcinoma cells cultured in two-dimensional (2D) and three-dimensional (3D) formats. It was shown that both unsubstituted calixarenes decrease the viability of tumor cells; calix[4]arene and calix[6]arene exhibited a cytostatic and a cytotoxic effect, respectively. Sulfated derivatives of calixarenes did not have a pronounced toxic effect on HT-29 cells. However, due to their high hydrophilicity and the ability to form adducts with various therapeutic molecules, they can be used for delivery of anticancer drugs. calixarenes, cytotoxicity, HT-29 cells, 2D cell culture, 3D cell culture The work was financially supported by the Russian Science Foundation (project no. 19-15-00397).

scholarly journals Biological Activity and Chemical Constituents of Essential Oil and Extracts of Murraya microphylla

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000
Author(s):  
Hai-Ning Lv ◽  
Ke-Wu Zeng ◽  
Bing-Yu Liu ◽  
Yun Zhang ◽  
Peng-Fei Tu ◽  
...  
Keyword(s):  
Essential Oil ◽  
Human Cancer ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Cytotoxic Activities ◽  
Active Components ◽  
Human Cancer Cell Lines ◽  
Total Oil ◽  
Promising Development ◽  
Carbazole Alkaloids

Murraya microphylla is the most closely related species to M. koenigii (Curry tree). Inspired by the traditional effects of M. koenigii, the antioxidant, anti-inflammatory, and cytotoxic activities of the essential oil and extracts of M. microphylla were evaluated for the first time. The light petroleum and chloroform extracts were found to be able to scavenge DPPH free radicals, inhibit linoleic acid peroxidation, and nitric oxide production, as well as to present cytotoxicity to the human cancer cell lines HepG2, Bel7402, Bel7403, and Hela, but the essential oil only showed moderate activities. Chemical analysis of the active extracts by LC-DAD-MSn indicated that carbazole alkaloids were the main constituents. GC-MS analysis of the essential oil resulted in identification of 91 constituents, representing 96.9% of the total oil, with ( E)-caryophyllene (18.4%) and terpinen-4-ol (12.6%) as the major constituents. These results demonstrate that M. microphylla has similar biological activities, as well as chemical constituents to M. koenigii, and the carbazole alkaloids were disclosed to be the main potential active components. A promising development as a flavor and potential therapeutic agent could thus be predicated for this plant.

scholarly journals Comparative Antiproliferative activity of aerial parts of few Apocynaceae plants in HepG2, HT29 and SK-OV3 Human cancer cell lines

2019 ◽  
Vol 9 (4-s) ◽  
pp. 1195-1202
Author(s):  
Nirmala Devi ◽  
Ajay Kumar Gupta ◽  
Sunil Kumar Prajapati
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Srb Assay ◽  
Human Cancer Cell Lines ◽  
Aerial Parts ◽  
Carissa Carandas ◽  
Ht 29

Aims: Apocynaceae family is the 5th largest medicinal plant family rich in potent secondary metabolites such as Alkaloids, Cardiac glycosides,Terpenoids, irridoid/secoirridoids, flavonoids and Phenolic contents. The present study was aimed to evaluate and compare in-vitroantiproliferative activity of three plants of this family.Methods: Aerial parts of Carissa carandas Linn. (C), Nerium indicum Mill. (N) and Wrightia tinctoria RBr. (W), were collected and dried. Thepowdered drugs were extracted in Ethanol (1), 60% Ethanol (2) and Water (3). Estimation of Phytoconstituents performed using standardmethods. In-vitro cytotoxic activity performed using Sulphorhodamine B (SRB) assay in HepG2, HT29 and SKOV3 human cancer cell lines takingAdriamycin (ADR) as standard. For extracts, GI50 value ≤ 20μg/ml was considered to demonstrate activity.Results: For HepG2 cell line graphs and photomicrographs showed GI50 value as ADR=39.79, C1=2.5, N2=66.3, N3<10 and C2=C3= N1=W1-3>80. Also TGI for C1>80. The extracts, C1, C2, N1, N2, and N3 were found to possess activity against HepG2.These extracts were screened onHT 29 and SKOV3cell lines. The GI50 value observed was<10 for C1, N2, N3 and ADR in HT 29 and <10 for N3 and ADR in SK OV3 cell lines.Thus it was found that aqueous extract of Nerium indicum (N3) and Ethanolic extract of Carissa carandas (C1) were most cytotoxic extractsagainst all three cell lines.Conclusions: our study establishes that Apocynaceae family plants could be an important anticancer lead and could serve as Botanical drug forneoplasia.Keywords: Apocynaceae, SRB Assay, Phytoconstituents, Anticancer drug screening models, Hep G2, HT 29, SK-OV3, HCC.

scholarly journals SELENOT–Knockdown Leads to Reducing the Expression of Key Enzymes of ERAD–System in Cancer Cells Under ER–Stress

2021 ◽  
Author(s):  
M. V. Goltyaev ◽  
E. V. Blinova ◽  
E. G. Varlamova
Keyword(s):  
Er Stress ◽  
Mrna Expression ◽  
Colorectal Adenocarcinoma ◽  
Human Cancer ◽  
Redox Homeostasis ◽  
Marker Genes ◽  
Human Cancer Cell Lines ◽  
Stress Markers ◽  
Methylseleninic Acid ◽  
Number Of Genes

Abstract SELENOT is one of the seven selenoproteins localized in the ER. The purpose of this work was to study the effect of SELENOT–knockdown on mRNA expression of a large number of genes (ER–stress markers, physiological partners of SELENOT, ER–resident selenoproteins, other selenoproteins) under conditions of ER–stress caused by both selenium–containing compounds (sodium selenite and methylseleninic acid) and non–selenium–containing compounds (dithiothriitol) by the example of two human cancer cell lines A–172 (human glioblastoma) and Caco–2 (human colorectal adenocarcinoma). In the course of this work, it was found that SELENOT–knockdown does not significantly affect viability and proliferative properties, redox homeostasis in A–172 and Caco–2 cells and the acquisition of signs of normal cells by them, does not significantly affect the expression of ER–stress marker genes, ER–resident selenoproteins, with the exception of DIO2 and SELENOM. But it has a significant effect on reducing the levels of mRNA expression of AMFR and RNF5 are important enzymes of the ERAD–system, disrupting its work and leading to the accumulation of proteins with incorrect folding, thereby only aggravating ER stress.

scholarly journals Full Structural Characterization of Homoleptic Complexes of Diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1598 ◽  
Author(s):  
William Meza-Morales ◽  
M. Mirian Estévez-Carmona ◽  
Yair Alvarez-Ricardo ◽  
Marco A. Obregón-Mendoza ◽  
Julia Cassani ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Metal Complexes ◽  
Single Crystal ◽  
Cytotoxic Activity ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the β-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the β-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 μM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds.

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