scholarly journals Cytotoxic Withanolides from the Whole Herb of Physalis angulata L.

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1608 ◽  
Author(s):  
Qinghong Meng ◽  
Jiajia Fan ◽  
Zhiguo Liu ◽  
Xiwen Li ◽  
Fangbo Zhang ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Cytotoxic Activities ◽  
A549 Cell Line ◽  
Flow Cytometric ◽  
Whole Plant ◽  
P388 Cell ◽  
Physalis Angulata ◽  
New Compounds ◽  
Solanaceae Family

Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. Two new withanolides (1–2), together with six known analogues (3–8), were isolated from the whole plant of Physalis angulata L. The structures of these new compounds were determined on the basis of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The withanolides exhibited strong cytotoxic activities against A549, Hela and p388 cell lines. Furthermore, compounds 1 and 2 induced typical apoptotic cell death in A549 cell line according to the evaluation of the apoptosis-inducing activity by flow cytometric analysis.

scholarly journals Three New Cytotoxic Withanolides from the Chinese Folk Medicine Physalis angulata

2015 ◽  
Vol 10 (12) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Cai-Yun Gao ◽  
Ting Ma ◽  
Jun Luo ◽  
Ling-Yi Kong
Keyword(s):  
Cell Line ◽  
Folk Medicine ◽  
2D Nmr ◽  
Cytotoxic Activities ◽  
Spectroscopic Techniques ◽  
Aerial Parts ◽  
Physalis Angulata ◽  
The Absolute ◽  
New Compounds

Physagulides M-O, three new withanolides (1–3), were isolated from the aerial parts of Physalis angulata L. Their structures were elucidated through extensive spectroscopic techniques, including 1D and 2D NMR, and HRESIMS. The absolute configurations (22- R) of these new compounds were determined by CD analysis. Compounds 1 and 3 showed significant selective cytotoxic activities on the MG-63 cell line, with IC50 values of 4.28 and 5.44 μM, respectively.

scholarly journals Cytolethal Distending Toxin Induces Caspase-Dependent and -Independent Cell Death in MOLT-4 Cells

2008 ◽  
Vol 76 (10) ◽  
pp. 4783-4791 ◽  
Author(s):  
Masaru Ohara ◽  
Tomonori Hayashi ◽  
Yoichiro Kusunoki ◽  
Kei Nakachi ◽  
Tamaki Fujiwara ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Population ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Membrane Disruption ◽  
Classical Pathway ◽  
Cytolethal Distending Toxin ◽  
Flow Cytometric ◽  
General Caspase Inhibitor

ABSTRACT Cytolethal distending toxin (CDT) induces apoptosis using the caspase-dependent classical pathway in the majority of human leukemic T cells (MOLT-4). However, we found the process to cell death is only partially inhibited by pretreatment of the cells with a general caspase inhibitor, z-VAD-fmk. Flow cytometric analysis using annexin V and propidium iodide showed that a 48-h CDT treatment decreased the living cell population by 35% even in the presence of z-VAD-fmk. z-VAD-fmk completely inhibited caspase activity in 24 h CDT-intoxicated cells. Further, CDT with z-VAD-fmk treatment clearly increased the cell population that had a low level of intracellular reactive oxygen. This is a characteristic opposite to that of caspase-dependent apoptosis. Overexpression of bcl2 almost completely inhibited cell death using CDT treatment in the presence of z-VAD-fmk. The data suggest there are at least two different pathways used in CDT-induced cell death: conventional caspase-dependent (early) apoptotic cell death and caspase-independent (late) death. Both occur via the mitochondrial membrane disruption pathway.

Regulation of oxidative stress–mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice

2008 ◽  
Vol 27 (1) ◽  
pp. 55-63 ◽  
Author(s):  
S Prasad ◽  
N Kalra ◽  
S Srivastava ◽  
Y Shukla
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Agent ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Regulatory Proteins ◽  
Diallyl Sulfide ◽  
Flow Cytometric ◽  
Polycyclic Aromatic ◽  
Carcinogenic Polycyclic Aromatic Hydrocarbon ◽  
Sulfur Containing

Diallyl sulfide, a sulfur-containing volatile compound present in garlic ( Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, apoptosis-inhibiting effects of diallyl sulfide against a carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethyl benz(a)anthracene (DMBA), in Swiss albino mice were observed. The animals were given either 250 μg/mouse or 500 μg/mouse of diallyl sulfide for 1 week after a single intragastric dose of 7,12-dimethyl benz(a)anthracene (50 mg/kg body weight). Results showed that diallyl sulfide supplementation effectively protects against 7,12-dimethyl benz(a)anthracene—induced oxidative stress, characterized by restored antioxidant enzyme levels (up to 64%) and lipid peroxidation (up to 25%). Flow cytometric analysis showed a reduction in apoptotic cell population in hypodiploid region in diallyl sulfide–supplemented animals. Inhibition of apoptosis was preceded by decrease in reactive oxygen species levels and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In 7,12-dimethyl benz(a)anthracene–exposed animals, downregulation (~30%) of antiapoptotic Bcl-2 and upregulation (~60%) of pro-apoptotic Bax proteins were observed. These alterations were restored significantly by diallyl sulfide supplementation, indicating inhibition of apoptosis. Thus, these results show that diallyl sulfide provides protection against oxidative damage induced by 7,12-dimethyl benz(a)anthracene in mouse liver and may be an effective chemopreventive and therapeutic agent by modulating expression of cell-growth regulatory proteins.

scholarly journals Actinobacillus actinomycetemcomitansLeukotoxin Induces Apoptosis in HL-60 Cells

1998 ◽  
Vol 66 (9) ◽  
pp. 4474-4483 ◽  
Author(s):  
Jonathan Korostoff ◽  
Jian Fei Wang ◽  
Irene Kieba ◽  
Mark Miller ◽  
Bruce J. Shenker ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Inflammatory Cells ◽  
Target Cells ◽  
Light Scatter ◽  
Flow Cytometric ◽  
Final Population ◽  
Cellular Debris ◽  
Phosphatidylserine Translocation

ABSTRACT Actinobacillus actinomycetemcomitans leukotoxin (Ltx) is a member of the repeats-in-toxin (RTX) family of pore-forming toxins and kills human immune cells. Currently, it remains unclear whether toxin-mediated killing of target cells involves the induction of necrosis or apoptosis. Therefore, the goal of this investigation was to determine whether Ltx is capable of causing apoptotic cell death in toxin-sensitive promyelocytic HL-60 cells. Multiparameter flow cytometric analysis of toxin-treated cells stained with Hoechst 33258 (or 33342) and 7-aminoactinomycin D allowed us to identify four populations: viable cells, early apoptotic cells, late apoptotic and/or secondarily necrotic cells, and a final population that was composed of cellular debris. Compared with control cells, HL-60 cells treated with Ltx exhibited a gradual decrease in forward light scatter with a coincident increase in side light scatter, indicative of a decrease in cell size and organelle condensation, respectively. Additional experiments demonstrated that Ltx-treated cells showed evidence of internucleosomal DNA fragmentation and phosphatidylserine translocation. The results of our studies clearly demonstrate that Ltx can kill HL-60 cells by inducing apoptosis. We hypothesize that elimination of acute inflammatory cells via this mechanism plays a critical role in the pathogenesis of diseases caused by A. actinomycetemeomitans.

scholarly journals A Novel Cytotoxic Physalin from Physalis angulata

2017 ◽  
Vol 12 (10) ◽  
pp. 1934578X1701201
Author(s):  
Jia-Jia Fan ◽  
Xia Liu ◽  
Xi-Long Zheng ◽  
Hai Yu Zhao ◽  
Huan Xia ◽  
...  
Keyword(s):  
Spectroscopic Data ◽  
Hepatoma Cells ◽  
Cytotoxic Activities ◽  
Mammary Cells ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Whole Plant ◽  
Bioassay Guided Fractionation ◽  
Physalis Angulata ◽  
Mcf 7

Bioassay-guided fractionation from the whole plant of Physalis angulata led to the isolation of a novel physalin, 25-hydroxylisophysalin B (1), together with three megastigmane glucosides (2-4) and eight known physalins (5-12). The structure of compound 1 was elucidated by analysis of spectroscopic data. All of the compounds exhibited cytotoxic activities against MCF-7 human mammary cells and HepG2 human hepatoma cells.

scholarly journals Naringenin inhibits human breast cancer cells (MDA-MB-231) by inducing programmed cell death, caspase stimulation, G2/M phase cell cycle arrest and suppresses cancer metastasis

2021 ◽  
Vol 67 (2) ◽  
pp. 8-13
Author(s):  
Zhaozhen Qi ◽  
Shuangxi Kong ◽  
Shunyu Zhao ◽  
Qiu Tang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
M Phase

The current study was designed to unveil the anticancer effects of naringenin against breast cancer MDA-MB-231 cells. Cytotoxic effects were estimated via MTT viability assay. Clonogenic assay was performed to assess clonogenic potential of MDA-MB-231 cells. Apoptosis was examined via AO/EB staining, quantified via annexin V/PI staining and western blotting was performed to monitor apoptosis allied protein expressions. Cell cycle was analyzed through flow cytometric analysis. Transwell chambers assay was executed for determination of cell migration and cell invasion tendency of MDA-MB-231 breast cancer cells. Results indicated significant anticancer potential of naringenin drug against MDA-MB-231 cells. On evaluation of cell proliferation rate of breast cancer cells by MTT assay, it was observed that naringenin inhibited proliferation rate in dose as well as time dependent manner. AO/EB staining assay revealed potential morphological changes indicating apoptotic cell death. Annexin V/PI staining assay revealed increased apoptotic cell percentage with increased drug doses. The apoptosis inducing potential of naringenin drug was observed to be mediated via caspase activation. Flow cytometric analysis predicted cell cycle arrest at G2/M phase of cell cycle. Further cell migration as well as cell invasion tendency of MDA-MB-231 cells was reduced to minimum upon application of naringenin drug.

scholarly journals A Triazole Hybrid of Neolignans as a Potential Antileishmanial Agent by Triggering Mitochondrial Dysfunction

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 37 ◽  
Author(s):  
Carla Cardozo Pinto de Arruda ◽  
Daiana de Jesus Hardoim ◽  
Yasmin Silva Rizk ◽  
Celeste da Silva Freitas de Souza ◽  
Tânia Zaverucha do Valle ◽  
...  
Keyword(s):  
Cell Death ◽  
Direct Action ◽  
Flow Cytometric Analysis ◽  
Tem Analysis ◽  
Methylenedioxy Group ◽  
Highly Active ◽  
Flow Cytometric ◽  
Transmission Electron ◽  
New Compounds ◽  
Intracellular Amastigote

In the search for new compounds with antileishmanial activity, we synthesized a triazole hybrid analogue of the neolignans grandisin and machilin G (LASQUIM 25), which was previously found highly active against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. In this work, we investigated the leishmanicidal effects of LASQUIM 25 to identify the mechanisms involved in the cell death of L. amazonensis promastigotes. Transmission electron microscopy (TEM) analysis showed marked effects of LASQUIM 25 (IC50 = 7.2 µM) on the morphology of promastigote forms, notably on mitochondria. The direct action of the triazole derivative on the parasite was noticed over time from 2 h to 48 h, and cells displayed several ultrastructural alterations characteristic of apoptotic cells. Also, flow cytometric analysis (FACS) after TMRE staining detected changes in mitochondrial membrane potential after LASQUIM 25 treatment (64.83% labeling versus 83.38% labeling in nontreated cells). On the other hand, FACS after PI staining in 24 h-treatment showed a slight alteration in the integrity of the cell membrane, a necrotic event (16.76% necrotic cells versus 3.19% staining in live parasites). An abnormal secretion of lipids was observed, suggesting an exocytic activity. Another striking finding was the presence of autophagy-related lysosome-like vacuoles, suggesting an autophagic cell death that may arise as consequence of mitochondrial stress. Taken together, these results suggest that LASQUIM 25 leishmanicidal mechanisms involve some degree of mitochondrial dysregulation, already evidenced by the treatment with the IC50 of this compound. This effect may be due to the presence of a methylenedioxy group originated from machilin G, whose toxicity has been associated with the capacity to generate electrophilic intermediates.

Synthesis of platinum(II) complexes of 2-cycloalkyl-substituted benzimidazoles and their cytotoxic effects

2015 ◽  
Vol 70 (9-10) ◽  
pp. 243-250
Author(s):  
A. Berna Özçelik ◽  
Fatma Gümüş ◽  
Rahşan Ilıkçı Sağkan ◽  
Uğur Muşabak
Keyword(s):  
Cell Viability ◽  
Hela Cells ◽  
Cytotoxic Effect ◽  
Flow Cytometric Analysis ◽  
Cytotoxic Activities ◽  
Cytotoxic Effects ◽  
Viability Test ◽  
Flow Cytometric ◽  
A Cell

Abstract Five novel Pt(II) complexes with some 2-cycloalkyl-substituted benzimidazole carrier-ligands were synthesized and evaluated for their in vitro cytotoxic activities against HeLa and OVCAR-3 cell lines. A cell viability test revealed that [dichloro-bis(2-cycloheptylbenzimidazole) platinum(II)] is less cytotoxic than cisplatin, and its cytotoxic effect can be compared with that of carboplatin. Flow cytometric analysis revealed that this complex at 117 μM concentration causes apoptosis in approx. 72 % of the OVCAR-3 cell population. In addition, the complex was found to cause an increase in the SubG1 population of both OVCAR-3 and HeLa cells and to cause less apoptosis in HeLa cells than cisplatin.

Apoptotic Effect of Novel Benzimidazole Derivatives Bearing Pyridyl/Pyrimidinyl Piperazine Moiety

2021 ◽  
Vol 21 ◽  
Author(s):  
Gulsen Çiftçi ◽  
Halide Edip Temel ◽  
Leyla Yurttaş
Keyword(s):  
Dna Synthesis ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Biological Activities ◽  
Flow Cytometric Analysis ◽  
Benzimidazole Derivatives ◽  
Cholinesterase Inhibition ◽  
Cytotoxic Activities ◽  
Nih 3T3

Background: Benzimidazole derivatives bearing pyridyl/pyrimidinyl piperazine moiety has attracted attention in medicinal chemistry and modern drug discovery since it exhibited a variety of biological activities, including anticancer activity. Objective: In this study, we have designed and synthesized novel 1-[2-oxo-2-(4-substituted phenyl)ethyl]benzimidazol-2-yl)methyl 4-(2-pyridyl/pyrimidin-2-yl)piperazine-1-carbodithioate derivatives (2a-m). We also investigated their anticancer activities against A549 lung adenocarcinoma and C6 rat glioma cell lines and selectivity against NIH/3T3 mouse embryonic fibroblast cell lines. Cholinesterase inhibition effects of these compounds were also measured to investigate the relationship between anticancer activity and cholinesterases. Method: The cytotoxic activities of these acquired thirteen final compounds were screened using MTT assay on A549, C6, and NIH/3T3 cell lines. Cell proliferation ELISA, BRDU (colorimetric) assay was used for measuring proliferation in replicative cells in which DNA synthesis occurs. Flow cytometric analysis was used for measuring apoptotic cell percentages, caspase 3 activity, and mitochondrial membrane depolarised cell percentages. Results: Compounds 2e, 2f, and 2k have been established as the most active antitumor agents with selective cytotoxicities (76.58±6.43, 55.13±5.75, and 32.94±3.02 µM respectively for A549; 86.48±3.60, 97.12±30.21, and 59.29±3.95 µM respectively for C6), high DNA synthesis inhibition rates and high apoptotic cell percentages on both cell lines. Conclusion: The results have shown that compounds 2e, 2f, and 2k have potential anticancer agents against A549 and C6 cell lines.

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