scholarly journals Synthesis of Ergosterol Peroxide Conjugates as Mitochondria Targeting Probes for Enhanced Anticancer Activity

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3307 ◽  
Author(s):  
Ming Bu ◽  
Hongling Li ◽  
Haijun Wang ◽  
Jing Wang ◽  
Yu Lin ◽  
...  
Keyword(s):  
Human Cancer ◽  
Fluorescent Imaging ◽  
Invasion And Migration ◽  
Human Cancer Cells ◽  
Ergosterol Peroxide ◽  
Intracellular Ros ◽  
M Phase ◽  
And Migration ◽  
Mitochondria Targeting ◽  
Mcf 7

Inspired by the significant bioactivity of ergosterol peroxide, we designed and synthesized four fluorescent coumarin and ergosterol peroxide conjugates 8a–d through the combination of ergosterol peroxide with 7-N,N-diethylamino coumarins fluorophore. The cytotoxicity of synthesized conjugates against three human cancer cells (HepG2, SK-Hep1, and MCF-7) was evaluated. The results of fluorescent imaging showed that the synthesized conjugates 8a–d localized and enriched mainly in mitochondria, leading to significantly enhanced cytotoxicity over ergosterol peroxide. Furthermore, the results of biological functions of 8d showed that it could suppress cell colony formation, invasion, and migration; induce G2/M phase arrest of HepG2 cells, and increase the intracellular ROS level.

scholarly journals Gambogic Acid Lysinate Induces Apoptosis in Breast Cancer MCF-7 Cells by Increasing Reactive Oxygen Species

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yong-Zhan Zhen ◽  
Ya-Jun Lin ◽  
Kai-Ji Li ◽  
Xiao-Shan Yang ◽  
Yu-Fang Zhao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Human Cancer ◽  
Signal Pathway ◽  
Gambogic Acid ◽  
Oxygen Species ◽  
Human Cancer Cells ◽  
Intracellular Ros ◽  
Mcf 7

Gambogic acid (GA) inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited.Objectives.To investigate the antitumor activity of gambogic acid lysinate (GAL) and its mechanism.Methods.Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot.Results.GAL inhibited the proliferation of MCF-7 cells with IC50values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L). GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3.Conclusions.GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.

scholarly journals Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism

2021 ◽  
Author(s):  
Yuki Konno ◽  
Ami Maruyama ◽  
Masaru Tomita ◽  
Hideki Makinoshima ◽  
Joji Nakayama
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Bark Extract ◽  
Glycolytic Metabolism ◽  
Cinnamon Bark ◽  
Metastatic Dissemination ◽  
Invasion And Migration ◽  
Human Cancer Cells ◽  
And Migration

AbstractMetastasis, a leading contributor to the morbidity of cancer patients, occurs through multiple steps. As each of these steps is promoted by different molecular mechanisms, blocking metastasis needs to target each of these steps. Here we report that cinnamon bark extract (CBE) has a suppressor effect on metastatic dissemination of cancer cells. Though a zebrafish embryo screen which utilizes conserved mechanisms between metastasis and zebrafish gastrulation for identifying anti-metastasis drugs, CBE was identified to interfere with gastrulation progression of zebrafish. A zebrafish xenotransplantation model of metastasis validated that CBE suppressed metastatic dissemination of human cancer cells (MDA-MB-231). Interestingly, quantitative metabolome analyses revealed that CBE-treated MDA-MB-231 cells disrupted the production of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which are intermediate metabolites of glycolytic metabolism. CBE decreased the expression of hexokinase 2 (HK2), which catalyzes G6P production, and pharmacological inhibition of HK2 suppressed cell invasion and migration of MDA-MB-231 cells. Taken together, CBE suppressed metastatic dissemination of human cancer cells by inhibiting glycolytic metabolism.

scholarly journals Antioxidants, Phytochemicals, and Cytotoxicity Studies onPhaleria macrocarpa(Scheff.) Boerl Seeds

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Ma Ma Lay ◽  
Saiful Anuar Karsani ◽  
Behrooz Banisalam ◽  
Sadegh Mohajer ◽  
Sri Nurestri Abd Malek
Keyword(s):  
Human Cancer ◽  
Cytotoxic Effects ◽  
Nutritional Values ◽  
Water Fraction ◽  
Human Cancer Cells ◽  
Fiber Protein ◽  
Cytotoxicity Studies ◽  
Normal Human ◽  
Lung Cell Line ◽  
Mcf 7

In recent years, the utilization of certain medicinal plants as therapeutic agents has drastically increased.Phaleria macrocarpa(Scheff.) Boerl is frequently used in traditional medicine. The present investigation was undertaken with the purpose of developing pharmacopoeial standards for this species. Nutritional values such as ash, fiber, protein, fat, and carbohydrate contents were investigated, and phytochemical screenings with different reagents showed the presence of flavonoids, glycosides, saponin glycosides, phenolic compounds, steroids, tannins, and terpenoids. Our results also revealed that the water fraction had the highest antioxidant activity compared to the methanol extract and other fractions. The methanol and the fractionated extracts (hexane, chloroform, ethyl acetate, and water) ofP. macrocarpaseeds were also investigated for their cytotoxic effects on selected human cancer cells lines (MCF-7, HT-29, MDA-MB231, Ca Ski, and SKOV-3) and a normal human fibroblast lung cell line (MRC-5). Information from this study can be applied for future pharmacological and therapeutic evaluations of the species, and may assist in the standardization for quality, purity, and sample identification. To the best of our knowledge, this is the first report on the phytochemical screening and cytotoxic effect of the crude and fractionated extracts ofP. macrocarpaseeds on selected cells lines.

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.

scholarly journals Antiproliferative Benzoindazolequinones as Potential Cyclooxygenase-2 Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2261 ◽  
Author(s):  
Aurora Molinari ◽  
Alfonso Oliva ◽  
Marlene Arismendi-Macuer ◽  
Leda Guzmán ◽  
Waldo Acevedo ◽  
...  
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Antitumor Agents ◽  
Human Cancer ◽  
In Vitro Models ◽  
Cyclooxygenase 2 ◽  
Binding Energies ◽  
Human Cancer Cells ◽  
Mcf 7

Quinones and nitrogen heterocyclic moieties have been recognized as important pharmacophores in the development of antitumor agents. This study aimed to establish whether there was any correlation between the in silico predicted parameters and the in vitro antiproliferative activity of a family of benzoindazolequinones (BIZQs), and to evaluate overexpressed proteins in human cancer cells as potential biomolecular targets of these compounds. For this purpose, this study was carried out using KATO-III and MCF-7 cell lines as in vitro models. Docking results showed that these BIZQs present better binding energies (ΔGbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 measured in both cell lines (KATO-III: 0.72, 0.41, and 0.90; MCF-7: 0.79, 0.55, and 0.87 for Series I, II, and III, respectively). The results also indicated that compounds 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin values than the other derivatives. In silico drug absorption, distribution, metabolism, and excretion (ADME) properties of the three series were also analyzed and showed that several BIZQs could be selected as potential candidates for cancer pre-clinical assays.

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.

Nobiletin Inhibits Proliferation, Invasion, Migration and Angiogenesis in Colorectal Cancer Cells

2019 ◽  
Vol 9 (5) ◽  
pp. 662-667
Author(s):  
Jing Li ◽  
Zaijun Li ◽  
Fei Zheng
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Human Cancer ◽  
Cell Counting ◽  
Control Group ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Traditional Chinese Herbal Medicine ◽  
And Migration

Aim/Background: The nobiletin is a polymethoxyflavonoid isolated from citrus, which is a traditional Chinese herbal medicine. The nobiletin could inhibit the development of human cancer. However, the role of nobiletin in human colorectal cancer (CRC) remains unknown. The present study aimed to explore the nobiletin function in CRC cell proliferation, migration, invasion and angiogenesis as well as the occurrence mechanisms. Methods: The cell counting kit-8 assay (CCK-8 assay) and Brdu (5-brom-2-odeoxyuridine) staining assay were used to determine the effect of nobiletin on cell proliferation. The transwell assay and wound healing assay were used to assess cell invasion and migration. The western blot analysis was performed to determine the expression of VEGFA, Ang2, p65, p-p65, STAT3, p-STAT3 in CRC cell. Result: Compared with the control group (0 mg/L), the cell proliferation was increased in a dose-dependent manner with 10, 50, 100, 150 mg/L nobiletin for 48 h. The nobiletin inhibited cell invasion and migration and suppressed the expression of VEGFA and Ang2 to block angiogenesis in the colorectal cancer. In addition, we found that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis by suppression of NF-κB/STAT3 pathway. Conclusion: The study provided evidence that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis in the colorectal cancer.

The role of circCNIH4 in the adipocyte's effects on metastasis of breast cancer cells.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13086-e13086
Author(s):  
Xiu Chen ◽  
Jinhai Tang
Keyword(s):  
Breast Cancer ◽  
Wound Healing ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
Non Invasive ◽  
In Vivo Experiments ◽  
And Migration ◽  
Mcf 7

e13086 Background: Obesity is associated with the risk of breast cancer(BCa) incidence and development. However, biological changes in obesity BCa individuals are still uncertain. Nowadays, circCNIH4, one of novel non-coding RNAs, was found to be a non-invasive biomarker in cancers. Methods: We verified the cancer-promoting role of obesity in BCa patients by comparing BMI indexes of 33 BCa and 44 benign tumor patients. Then we cocultured viscera adipose cells(HPA-v) and BCa cells(MCF-7/H and MDA-MB-231/H) to confirm the function of adipocytes on metastasis of BCa cells through wound healing, transwell assays. In vivo experiments were also performed. We analyzed the expression level of circCNIH4 in MCF-7/H, MDA-MB-231/H and different subtypes of BCa cells by quantitative polymerase chain reaction. Simultaneously, we identified inhibited effects of circCNIH4 on metastasis of BCa cells by wound healing, transwell assays and verified the location of circCNIH4 by FISH. Luciferase Assay was used to detect harbored miRNA. Rescue experiments were then applied. Results: We found the BMI of BCa patients(24.37±2.51) was much higher than benign patients(22.97±2.91). Metastasis of BCa cells were obviously promoted after in vitro and in vivo experiments. Then we found the expression of circCNIH4 in MCF-7/H and MDA-MB-231/H were down-regulated 0.71 and 0.52 than that in MCF-7 and MDA-MB-231. Also, circCNIH4 was positively correlated with less aggressive types of BCa cells. Overexpression of circCNIH4 in MDA-MB-231 could suppress cell invasion and migration, while silencing of it in MCF-7 promoted cell invasion and migration. The FISH assay demonstrated that circCNIH4 mainly located in the cytoplasm and might function as a “sponge” for miRNA. MiR-135b functioned as a tumor promoter gene from data of 93 BCa patients (HR = 2.27; 1.01 − 5.12), and it could be captured by circCNIH4 via luciferase and rescued assays. Conclusions: In this study, we revealed that BMI or viscera adipocytes could deteriorate prognosis of BCa and circCNIH4 could be a novel biomarker for non-invasive BCa. In details, circCNIH4 mainly suppressed the adipocyte's pro-metastasis effects on BCa by capturing miR-135b.

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.

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