scholarly journals Inhibition of NADPH Oxidases Activity by Diphenyleneiodonium Chloride as a Mechanism of Senescence Induction in Human Cancer Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1248
Author(s):  
Katarzyna Piszczatowska ◽  
Dorota Przybylska ◽  
Ewa Sikora ◽  
Grażyna Mosieniak
Keyword(s):  
Cancer Cells ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Cell Metabolism ◽  
Human Colon ◽  
Nadph Oxidases ◽  
Human Colon Cancer ◽  
Inhibition Of Proliferation ◽  
Human Cancer Cells ◽  
Mcf 7

NADPH oxidases (NOX) are commonly expressed ROS-producing enzymes that participate in the regulation of many signaling pathways, which influence cell metabolism, survival, and proliferation. Due to their high expression in several different types of cancer it was postulated that NOX promote tumor progression, growth, and survival. Thus, the inhibition of NOX activity was considered to have therapeutic potential. One of the possible outcomes of anticancer therapy, which has recently gained much interest, is cancer cell senescence. The induction of senescence leads to prolonged inhibition of proliferation and contributes to tumor growth restriction. The aim of our studies was to investigate the influence of low, non-toxic doses of diphenyleneiodonium chloride (DPI), a potent inhibitor of flavoenzymes including NADPH oxidases, on p53-proficient and p53-deficient HCT116 human colon cancer cells and MCF-7 breast cancer cells. We demonstrated that the temporal treatment of HCT116 and MCF-7 cancer cells (both p53 wild-type) with DPI caused induction of senescence, that was correlated with decreased level of ROS and upregulation of p53/p21 proteins. On the contrary, in the case of p53−/− HCT116 cells, apoptosis was shown to be the prevailing effect of DPI treatment. Thus, our studies provided a proof that inhibiting ROS production, and by this means influencing ROS sensitive pathways, remains an alternative strategy to facilitate so called therapy-induced senescence in cancers.

Induction of Apoptic Features in Human Colon Cancer Cells After Exposure to Specific Vitamin Combinations

2000 ◽  
Vol 6 (S2) ◽  
pp. 892-893
Author(s):  
B. Brown ◽  
K. R. Garvin ◽  
B. G. Hughes ◽  
M. D. Standing ◽  
K. L. O'Neill ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Human Cancer Cells ◽  
Induction Of Apoptosis ◽  
Programed Cell Death ◽  
Ht 29

Proper nutrition and vitamin consumption have long been associated with lower risks for many human cancers. Data from recent studies have suggested that exposure to antioxidant vitamins and vitamin combinations can induce genetic programed cell death, apoptosis, in human cancer cells. ‘“3 In this study, we report on the induction of apoptosis in HT-29 human colon adenocarcinoma cells after exposure to low doses of 13- c/s-retinoic acid (RA) and vitamin E succinate (VES). Induction of apoptosis was seen only in cancerous colon cells and not in normal human colon cells when exposed to RA and VES in combination, but not when exposed to either vitamin alone.Cultures of HT-29 cells were seeded in 6 well plates at 10,000 cells/well and grown at 37°C, 5% C02 in RPMI 1640 medium supplemented with 10% fetal bovine serum.

Identification of terpenoids from Rubus corchorifolius L. f. leaves and their anti-proliferative effects on human cancer cells

2017 ◽  
Vol 8 (3) ◽  
pp. 1052-1060 ◽  
Author(s):  
Xuexiang Chen ◽  
Zili Gao ◽  
Mingyue Song ◽  
Wen Ouyang ◽  
Xian Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Inhibitory Effects ◽  
Human Colon Cancer ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Human Colon Cancer Cells

Two novel and four known terpenoids were isolated and identified fromRubus corchorifoliusL. f. leaves. Two exhibited strong inhibitory effects on HCT116 human colon cancer cells, causing cell cycle arrest and apoptosis.

scholarly journals Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Iván González-Chavarría ◽  
Felix Duprat ◽  
Francisco J. Roa ◽  
Nery Jara ◽  
Jorge R. Toledo ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Human Cancer ◽  
Ros Generation ◽  
Active Components ◽  
Total Extract ◽  
Human Cancer Cells ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Membrane Depolarization ◽  
Mcf 7

Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. β-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (µg/mL) of 40, 4.7, and 5 µg/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The β-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-β-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 µM, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the β-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.

scholarly journals Synthetic sphingolipid analogs and anti-cancer drugs synergistically induced human colon and pancreatic cancer cell death through inhibiting ceramide metabolism

2021 ◽  
Author(s):  
Jing Song ◽  
Arie Dagan
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Colon ◽  
Cancer Drugs ◽  
Human Cancer Cells ◽  
Low Concentrations ◽  
Anti Cancer ◽  
Sphingolipid Analogs

AbstractCeramide metabolism is a potential target for anti-cancer therapy. Studies show that chemotherapeutic agents can induce apoptosis and it is mediated by ceramide. Synthesized sphingolipid analogs can induce cell death in human lymphocytes and leukemia cells. By screening a group of synthetic sphingolipid analogs, we found that low concentrations of AD2750 and AD2646 induced cell death in human cancer cells by preventing ceramide from converting to sphingomyelin, individually or in combination with commercial cancer drugs. The combination of low concentrations of Taxol and AD2750 or AD2646 significantly increased cell death on human colon cancer cells (HT29). Co-administering low concentrations of Doxorubicin with AD2750 or AD2646 elevated cellular toxicity on human pancreatic cancer cells (CRL1687). This synergistic effect is related to the elevated cellular ceramide. Combining AD2750 or AD2646 with chemotherapy drugs can be used to manipulate ceramide and sphingomyelin metabolism, potentially to affect the growth of human cancer cells and increase the effectiveness of anti-cancer drugs on killing cancer cells.

scholarly journals Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 888 ◽  
Author(s):  
Chen ◽  
Liu ◽  
Huang ◽  
Li ◽  
Zhao ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cancer Cells ◽  
Cell Fusion ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Daughter Cells ◽  
Mitotic Slippage ◽  
Polyploid Cells ◽  
Mcf 7

Multipolar divisions of heated cells has long been thought to stem from centrosome aberrations of cells directly caused by heat stress. In this paper, through long-term live-cell imaging, we provide direct cellular evidences to demonstrate that heat stress can promote multiple multipolar divisions of MGC-803 and MCF-7 cells. Our results show that, besides facilitating centrosome aberration, polyploidy induced by heat stress is another mechanism that causes multipolar cell divisions, in which polyploid cancer cells engendered by mitotic slippage, cytokinesis failure, and cell fusion. Furthermore, we also find that the fates of theses polyploid cells depend on their origins, in the sense that the polyploid cells generated by mitotic slippage experience bipolar divisions with a higher rate than multipolar divisions, while those polyploid cells induced by both cytokinesis failure and cell fusion have a higher frequency of multipolar divisions compared with bipolar divisions. This work indicates that heat stress-induced multiple multipolar divisions of cancer cells usually produce aneuploid daughter cells, and might lead to genetically unstable cancer cells and facilitate tumor heterogeneity.

scholarly journals One-Pot Multicomponent Synthesis and Cytotoxic Evaluation of Novel 7-Substituted-5-(1H-Indol-3-yl)Tetrazolo[1,5-a] Pyrimidine-6-Carbonitrile

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 255
Author(s):  
Mohamed A. A. Radwan ◽  
Fahad M. Alminderej ◽  
Hanem M. Awad
Keyword(s):  
Human Cancer ◽  
Human Colon ◽  
Human Lung Cancer ◽  
Multicomponent Synthesis ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was synthesized via a one-pot, three-multicomponent reaction of appropriate aldehydes, 1H-tetrazole-5-amine and 3-cyanoacetyl indole in catalytic triethylamine. The cytotoxic activity of the new synthesized tetrazolopyrimidine-6-carbonitrile compounds was investigated against HCT-116, MCF-7, MDA-MB-231, A549 human cancer cell lines and one human healthy normal cell line (RPE-1) using the MTT cytotoxicity assay. Compounds 4h, 4b, 4c, 4i and 4a showed potent anticancer activities against human colon cancer. Additionally, all the compounds showed potent anticancer activities on human lung cancer.

scholarly journals Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 977 ◽  
Author(s):  
Neena Panicker ◽  
Sameera Balhamar ◽  
Shaima Akhlaq ◽  
Mohammed Qureshi ◽  
Tania Rizvi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Annexin V ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Cell Death Pathways ◽  
Proliferative Effect ◽  
Mcf 7

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.

scholarly journals Design and Synthesis of Novel Dehydroepiandrosterone Analogues as Potent Antiproliferative Agents

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2243 ◽  
Author(s):  
Xing Huang ◽  
Qing-Kun Shen ◽  
Hong-Jian Zhang ◽  
Jia-Li Li ◽  
Yu-Shun Tian ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Human Cancer ◽  
Cytotoxic Effects ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Design And Synthesis ◽  
Ic50 Value ◽  
G2 Phase ◽  
Mcf 7

The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hela, HepG-2, BEL7402, MCF-7, and HCT116. Several of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound was (E)-3-hydroxy-16-((1-(4-iodophenyl)-1H-1,2,3-triazole-4-yl)methylene)-10,13-dimet-hyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14)-one (compound 2n), which showed considerably high antiproliferative activity in the HepG-2 cell line, with an IC50 value of 9.10 µM, and considerably high activity against the MCF-7 cell line, with an IC50 value of 9.18 µM. Flow cytometry assays demonstrated that compound 2n exerted antiproliferative effects by arresting cells in the G2 phase of the cell cycle and inducing apoptosis.

Synthesis, Characterization and Cytotoxic Effect of Some New Thiazolyl Hydrazone Derivatives of 1-Indanone

2021 ◽  
Vol 43 (2) ◽  
pp. 244-244
Author(s):  
Urooj Nazim Urooj Nazim ◽  
Silpa Narayanan Silpa Narayanan ◽  
Mohsin Ali Mohsin Ali ◽  
Khalid Mohammed Khan Khalid Mohammed Khan ◽  
Basharat Ali Basharat Ali ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Cancer ◽  
Human Colon ◽  
Human Leukemia ◽  
Spectroscopic Techniques ◽  
Human Colon Cancer ◽  
Human Cancer Cells ◽  
Anti Cancer ◽  
Derivatives Of ◽  
Cancer Activity

In the present study, a series of twelve thiazolyl hydrazone derivatives of 1-indanone was synthesized and characterized by various spectroscopic techniques such as UV-Visible, NMR, IR and Mass Spectrometry. All the synthesized target compounds were subjected to MTT assay for cytotoxicity screening and evaluation of their anti-cancer activity on various cell lines of human cancer including glioblastoma (SNB-19), prostate cancer (PC-3), Lung cancer (NCI-H460), human ovarian carcinoma (SK-OV-3 and IGROV-1), human leukemia (K-562) and human colon cancer(HCT116).Three synthesized compounds showed promising anti-cancer activity against the colon cancer cell HCT 116 cells with IC50 ranging from 1.25and#177;0.02 to 5.04and#177;0.2 and#181;M. On the other hand all the compounds didn’t show cytotoxic activity against other forms of human cancer cells.

Cytotoxic effect of Berberis libanotica roots extracts on human cancer cells and antioxidant activities

2017 ◽  
Vol 6 (6) ◽  
pp. 311-317
Author(s):  
Kamar Hamade ◽  
◽  
Louna Karam ◽  
Jean Habib ◽  
Raghida Abou Merhi ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Antioxidant Activities ◽  
Human Cancer ◽  
Medicinal Tree ◽  
Human Cancer Cells ◽  
Promising Source ◽  
Ht 29 ◽  
Mcf 7

In the present study, we evaluated the cytotoxic effect and the antioxidant activity of methanolic and ethanolic roots extracts obtained from Berberis libanotica a Lebanese medicinal tree. Cytotoxic activity was assessed on the colon cancer HT 29, HCT 116, Caco-2 and breast cancer MCF-7 and MDA-MB-231cell lines, using the MTT viability assay. Both extracts inhibited cancer cells proliferation in a doseand time depending manner without being cytotoxic against the normal MCF-10 cell line. Our results suggest that methanolic extract could induce a caspase-independent cell death in the colon and breast tumor cells HT 29 and MCF-7, respectively. DPPH and FRAP assays showed a moderate to strong antioxidant activity of the methanolic and ethanolic extracts with EC50 values of 0.13 ± 0.001 and 0.1± 0.002 mg/ml, respectively. Collectively, these findings suggest that Berberis libanotica roots could serve as a promising source of antioxidant and anticancer bioactive compounds.

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