Cadmium modulates H-ras expression and caspase-3 apoptotic cell death in breast cancer epithelial MCF-7 cells

In this study, the potential of an n-butanol fraction from Ricinus communis to prevent metastasis in MCF-7 breast cancer cells was investigated. The effect of the fraction on BUD-8 and MCF-7 cell viability was assessed using the MTT assay. Apoptotic cell death was analyzed by Hoechst staining assay. The antimetastatic effect of the fraction on MCF-7 cell was evaluated using the wound healing, adhesion and Boyden chamber invasion assays. Gelatin-zymography was used to assess the effect of the fraction on MMP-2 and MMP-9 activity. The expression profile of proteins implicated in metastasis and angiogenesis was determined using the human angiogenesis antibody array kit, following treatment with the fraction. BUD-8 cell viability was significantly reduced at concentrations between 300 and 500 µg/ml of the extract. In contrast, a significant reduction in cell viability was seen in MCF-7 cells treated with 400 to 500 µg/ml of the fraction. At sub-lethal concentrations (100 and 200 µg/ml) of the fraction, no nuclei morphological changes associated with apoptotic cell death were observed in MCF-7 cells. In addition, the fraction showed to have an inhibitory effect on MCF-7 cell migration, adhesion, invasiveness, and MMP-2 activity. Moreover, the fraction was seen to modulate the expression of several proteins, such as MMP-9, uPA, VEGF, and TGF-β1, playing a role in the metastasis process. This study demonstrates that the n-butanol fraction of R. communis can inhibit major steps of the metastatic cascade and modulate metastasis regulatory proteins. Thus, the fraction can be considered a potential source of antimetastatic agents that could be useful in the treatment of malignant cancers.

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Transcriptome Analysis Reveals HgCl2 Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22042006 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2006

Author(s):

Mi Jin Kim ◽

Jinhong Park ◽

Jinho Kim ◽

Ji-Young Kim ◽

Mi-Jin An ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Transcriptome Analysis ◽

Caspase 3 ◽

Apoptotic Cell ◽

Expression Patterns ◽

Nitrogen Compound ◽

Apoptotic Cell Death ◽

Mercury Chloride ◽

Rna Seq

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl2 on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl2 treatment causes inhibition of cell growth via cell cycle arrest at G0/G1- and S-phase. In addition, HgCl2 induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl2 treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl2 treatment. Altogether, these data show that HgCl2 induces apoptotic cell death through the dysfunction of mitochondria.

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Two steroidal saponins from Camassia cusickii induce L1210 cell death through the apoptotic mechanism

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y01-068 ◽

2001 ◽

Vol 79 (11) ◽

pp. 953-958 ◽

Cited By ~ 3

Author(s):

Ellyawati Candra ◽

Kimihiro Matsunaga ◽

Hironori Fujiwara ◽

Yoshihiro Mimaki ◽

Yutaka Sashida ◽

...

Keyword(s):

Cell Death ◽

Caspase 3 ◽

Apoptotic Cell ◽

Chromatin Condensation ◽

Flow Cytometric Analysis ◽

Apoptotic Cell Death ◽

Morphological Observation ◽

Steroidal Saponin ◽

Steroidal Saponins ◽

L1210 Cells

Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5α-spirostan-3β-yl 4-O-[2-O-[3-O- (α-L-rhamnopyranosyl)-β-D-glucopyranosyl]-3-O-[4-O-(α-L-rhamnopyranosyl)-β-D-glucopyranosyl]-β-D-glucopyranosyl]- β-D-galactopyranoside) and tigogenin hexasaccharide-2 (TGHS-2, (25R)-5α-spirostan-3β-yl 4-O-[2-O-[3-O- (β-D-glucopyranosyl)-β-D-glucopyranosyl]-3-O-[4-O-(α-L-rhamnopyranosyl)-β-D-glucopyranosyl]-β-D-glucopyranosyl]- β-D-galactopyranoside), were isolated from the fresh bulbs of Camassia cusickii. In murine leukemic L1210 cells, both compounds showed cytotoxicity with an EC50 value of 0.06 µM. The morphological observation revealed that TGHS-1 and TGHS-2 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. The cell death was confirmed to be apoptosis by Annexin V binding to phosphatidylserine in the cell membrane and excluding propidium iodide. A typical apoptotic DNA ladder and the cleavage of caspase-3 were observed after treatment with TGHS-1 and TGHS-2. In the presence of both the compounds, cells with sub-G1 DNA content were detected by flow cytometric analysis, indicating that TGHS-1 and TGHS-2 (each EC50 value of 0.1 µM) are the most powerful apoptotic saponins known. These results suggest that TGHS-1 and TGHS-2 induce apoptotic cell death through caspase-3 activation.Key words: steroidal saponin, tigogenin hexasaccharide, apoptosis, DNA fragmentation, murine leukemic L1210 cells.

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Abstract WP62: Enhanced Neuroprotection of Normobaric Oxygenation with Ethanol Conferred by Apoptosis Reduction in Acute Ischemic Stroke

Stroke ◽

10.1161/str.44.suppl_1.awp62 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Sweena Parmar ◽

Xiaokun Geng ◽

Changya Peng ◽

Murali Guthikonda ◽

Yuchuan Ding

Keyword(s):

Cell Death ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Caspase 3 ◽

Apoptotic Cell ◽

Neuroprotective Effect ◽

Apoptotic Cell Death ◽

Ethanol Administration ◽

Sprague Dawley ◽

Apoptotic Proteins

Objectives: Normobaric oxygenation (NBO) has been shown to provide neuroprotection in vivo and in vitro . Yet, a recent Phase 2 clinical trial investigating NBO therapy in acute ischemic stroke was terminated due to questionable therapeutic benefit. NBO therapy alone may be insufficient to produce improved outcomes. In our recent study, we demonstrated a strong neuroprotective effect of ethanol at a dose of 1.5 g/kg (equivalent to the human legal driving limit). In this study, we sought to identify whether low-dose ethanol administration enhances the neuroprotection offered by NBO and whether combined administration of NBO with ethanol is associated with reduced apoptosis. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. Ischemic animals received either an intraperitoneal injection of 1.0 g/kg ethanol, 2 h of 100% NBO, or both ethanol and NBO. The Cell Death Detection ELISA Assay (Roche) was performed to determine apoptotic cell death at 24 h after reperfusion. Levels of pro-apoptotic (Caspase-3, Bcl-2-associated X-BAX, and Apoptosis-Inducing Factor-AIF) and anti-apoptotic proteins (Bcl-2 and Bcl-xL) were determined by Western blot analysis at 3 and 24 h after reperfusion. Results: As expected, untreated ischemic rats had the highest apoptotic cell death. Combined NBO/ethanol therapy decreased cell death by 48%, as compared to 29% with ethanol and 22% with NBO. Similarly, combined NBO/ethanol therapy promoted the greatest expression of anti-apoptotic factors and the lowest expression of pro-apoptotic proteins at 3 h after reperfusion. This effect was maintained at 24 h and even more pronounced for AIF and Caspase-3. Conclusions: Given singularly, NBO and ethanol improved the degree of cell death, decreased the expression of pro-apoptotic proteins, and increased the expression of anti-apoptotic proteins. Yet, when administered together, their effects largely compounded. These results suggest a synergistic neuroprotection offered by NBO with ethanol, which may be attributed at least in part to their shared role in modulating neuronal apoptosis.

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The effect of continuous combined 17β-oestradiol and dihydrodydrogesterone on apoptotic cell death and proliferation of human breast cancer cells in vitro

European Journal of Cancer ◽

10.1016/s0959-8049(02)00293-9 ◽

2002 ◽

Vol 38 ◽

pp. 69-70 ◽

Cited By ~ 6

Author(s):

H.R Franke ◽

I Vermes

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Human Breast Cancer Cells ◽

Human Breast

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Plumbagin from a tropical pitcher plant (Nepenthes alata Blanco) induces apoptotic cell death via a p53-dependent pathway in MCF-7 human breast cancer cells

Food and Chemical Toxicology ◽

10.1016/j.fct.2018.11.040 ◽

2019 ◽

Vol 123 ◽

pp. 492-500 ◽

Cited By ~ 18

Author(s):

Umasankar De ◽

Ji Yeon Son ◽

Yukyoung Jeon ◽

Song-Yi Ha ◽

Yu Jin Park ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Pitcher Plant ◽

Dependent Pathway ◽

Mcf 7

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Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging

Physiological Genomics ◽

10.1152/physiolgenomics.00136.2003 ◽

2004 ◽

Vol 17 (1) ◽

pp. 21-30 ◽

Cited By ~ 134

Author(s):

Anna Csiszar ◽

Zoltan Ungvari ◽

Akos Koller ◽

John G. Edwards ◽

Gabor Kaley

Keyword(s):

Cell Death ◽

Coronary Arteries ◽

Caspase 3 ◽

Apoptotic Cell ◽

The Elderly ◽

Apoptotic Cell Death ◽

Caspase 9 ◽

No Donor ◽

Endothelial Apoptosis ◽

Age Related

Previously we demonstrated that aging in coronary arteries is associated with proinflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by enhancing endothelial apoptosis. To test this hypothesis we characterized proapoptotic alterations in the phenotype of coronary arteries of aged (26 mo old) and young (3 mo old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was an approximately fivefold increase in the number of apoptotic endothelial cells. In aged coronary arteries there was an increased expression of TNFα, TNFβ, and caspase 9 (microarray, real-time PCR), as well as increased caspase 9 and caspase 3 activity, whereas expression of TNFR1, TNFα-converting enzyme (TACE), Bcl-2, Bcl-X(L), Bid, Bax, caspase 8, and caspase 3 were unchanged. In vessel culture (18 h) incubation of aged coronary arteries with a TNF blocking antibody or the NO donor S-nitroso-penicillamine (SNAP) decreased apoptotic cell death. Incubation of young arteries with exogenous TNFα increased caspase 9 activity and elicited endothelial apoptosis, which was attenuated by SNAP. Inhibition of NO synthesis in cultured young coronary arteries also induced apoptotic cell death and potentiated the apoptotic effect of TNFα. Thus we propose that age-related upregulation of TNFα and caspase 9 and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to impaired endothelial function and ischemic heart disease in the elderly.

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