Bufalin Induces Apoptotic Cell Death in Human Nasopharyngeal Carcinoma Cells through Mitochondrial ROS and TRAIL Pathways

2019 ◽  
Vol 47 (01) ◽  
pp. 237-257 ◽  
Author(s):  
En-Yun Su ◽  
Yung-Lin Chu ◽  
Fu-Shin Chueh ◽  
Yi-Shih Ma ◽  
Shu-Fen Peng ◽  
...  
Keyword(s):  
Cell Death ◽  
Nasopharyngeal Carcinoma ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Chromatin Condensation ◽  
Apoptotic Cell Death ◽  
Dapi Staining ◽  
Human Nasopharyngeal Carcinoma ◽  
Associated Proteins

The aim of this study was to investigate the effects of bufalin on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Bufalin is a cardiotonic steroid and a key active ingredient of the Chinese medicine ChanSu. The extracts of Chansu are used for various cancer treatments in China. In the present study, bufalin induced cell morphological changes, decreased total cell viability and induced G2/M phase arrest of cell cycle in NPC-TW 076 cells. Results also indicated that bufalin induced chromatin condensation (cell apoptosis) and DNA damage by DAPI staining and comet assay, respectively. The induced apoptotic cell death was further confirmed by annexin-V/PI staining assay. In addition, bufalin also increased ROS and Ca[Formula: see text] production and decreased the levels of [Formula: see text]. Furthermore, the alterations of ROS, ER stress and apoptosis associated protein expressions were investigated by Western blotting. Results demonstrated that bufalin increased the expressions of ROS associated proteins, including SOD (Cu/Zn), SOD2 (Mn) and GST but decreased that of catalase. Bufalin increased ER stress associated proteins (GRP78, IRE-1[Formula: see text], IRE-1[Formula: see text], caspase-4, ATF-6[Formula: see text], Calpain 1, and GADD153). Bufalin increased the pro-apoptotic proteins Bax, and apoptotic associated proteins (cytochrome c, caspase-3, -8 and -9, AIF and Endo G) but reduced anti-apoptotic protein Bcl-2 in NPC-TW 076 cells. Furthermore, bufalin elevated the expressions of TRAIL-pathway associated proteins (TRAIL, DR4, DR5, and FADD). Based on these findings, we suggest bufalin induced apoptotic cell death via caspase-dependent, mitochondria-dependent and TRAIL pathways in human nasopharyngeal carcinoma NPC-TW 076 cells.

Licochalcone A induces apoptotic cell death via JNK/p38 activation in human nasopharyngeal carcinoma cells

2019 ◽  
Vol 34 (7) ◽  
pp. 853-860 ◽  
Author(s):  
Chun‐Yi Chuang ◽  
Cheng‐Ming Tang ◽  
Hsin‐Yu Ho ◽  
Chung‐Han Hsin ◽  
Chia‐Jui Weng ◽  
...  
Keyword(s):  
Cell Death ◽  
Nasopharyngeal Carcinoma ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Carcinoma Cells ◽  
Licochalcone A ◽  
Human Nasopharyngeal Carcinoma

scholarly journals Novel Synthesized N-Ethyl-Piperazinyl-Amides of C2-Substituted Oleanonic and Ursonic Acids Exhibit Cytotoxic Effects through Apoptotic Cell Death Regulation

2021 ◽  
Vol 22 (20) ◽  
pp. 10967
Author(s):  
Oxana Kazakova ◽  
Alexandra Mioc ◽  
Irina Smirnova ◽  
Irina Baikova ◽  
Adrian Voicu ◽  
...  
Keyword(s):  
Cell Death ◽  
Ex Vivo ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Cancer Cell Line ◽  
Apoptotic Cell Death ◽  
Dapi Staining ◽  
Amide Derivatives ◽  
Induced Apoptosis

A series of novel hybrid chalcone N-ethyl-piperazinyl amide derivatives of oleanonic and ursonic acids were synthesized, and their cytotoxic potential was evaluated in vitro against the NCI-60 cancer cell line panel. Compounds 4 and 6 exhibited the highest overall anticancer activity, with GI50 values in some cases reaching nanomolar values. Thus, the two compounds were further assessed in detail in order to identify a possible apoptosis- and antiangiogenic-based mechanism of action induced by the assessed compounds. DAPI staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that up-regulation of pro-apoptotic Bak gene combined with the down-regulation of the pro-survival Bcl-XL and Bcl-2 genes caused altered ratios between the pro-apoptotic and anti-apoptotic proteins’ levels, leading to overall induced apoptosis. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, suggesting that compounds may induce apoptotic cell death through targeted anti-apoptotic protein inhibition, as well. Ex vivo determinations showed that both compounds did not significantly alter the angiogenesis process on the tested cell lines.

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

2001 ◽  
Vol 79 (11) ◽  
pp. 953-958 ◽  
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.

scholarly journals Autocrine Growth Hormone (GH)-Mediated Triptolide Resistance Overcame by Metformin Co-Treatment in MDA-MB231 Breast Cancer Cells Through ER Stress Pathway

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 9
Author(s):  
Amani Abdulmunem ◽  
Pınar Obakan-Yerlikaya ◽  
Elif-Damla Arisan ◽  
Ajda Coker-Gurkan
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Autocrine Growth ◽  
Common Cancer

Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug resistance profile in breast cancer cell lines against chemotherapeutic drugs such as tamoxifen, mitomycin C, doxorubicin and curcumin. Triptolide, an active plant extract from Tripterygium wilfordii, has been shown to induce apoptotic cell death in various cancer cells such a prostate, colon, breast cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce autophagy, endoplasmic reticulum (ER) stress and apoptotic cell death in cancer cells. Our aim is to demonstrate the potential effect of metformin on triptolide-mediated drug resistance in autocrine GH expressing MDA-MB-231 breast cancer cells through Endoplasmic reticulum (ER) stress. Autocrine GH-mediated triptolide (20 nM) resistance overcame by metformin (2 mM) co-teatment in MDA-MB231 breast cancer cells through accelerating cell viability loss, growth inhibition compared to alone triptolide treatment. Combined treatment increased apoptotic cell death via CHOP activation, IRE1α upregulation. Consequently, we suggest that triptolide can be more effective with metformin combination in MDA-MB-231 GH+ drug resistant breast cancer cells.

Vascular Endothelium Is Severely Perturbed and Undergoes Apoptosis in Experimental Heatstroke in Primates.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3972-3972
Author(s):  
George T. Roberts ◽  
Muhammad A. Chishti ◽  
Fallah H. Al-Mohanna ◽  
Raafat M. El-Sayed ◽  
Abderezak Bouchama
Keyword(s):  
Cell Death ◽  
Endothelial Cell ◽  
Vascular Endothelium ◽  
Apoptotic Cell ◽  
Chromatin Condensation ◽  
Apoptotic Cell Death ◽  
Control Group ◽  
Tissue Sections ◽  
Endothelial Cell Death

Abstract Introduction: Ultrastructural evidence of endothelial cell (EC) injury has been associated with diffuse microvascular thrombosis in human heatstroke (HS). In vitro studies have also shown that heat stress accelerates apoptotic cell death. Using a recently described baboon model of heatstroke, we sought to examine pathological changes in the vascular endothelium and whether apoptosis is a mechanism of endothelial cell death. Hypothesis: Major structural vascular endothelium alterations occur in HS and apoptosis is a mechanism of endothelial cell death in HS. Methods: Anesthetized baboons (Papio hamadyras) were heat-stressed in a neonatal incubator maintained at 44 1.5 °C, until rectal temperature attained 42.5°C (moderate heatstroke; n =4) or systolic blood pressure fell to < 90 mm Hg (severe heatstroke n =4). Animals were resuscitated with normal saline and allowed to cool at room temperature. Four sham-heated animals served as control group. Spleen, liver, heart, kidney, gut, lung and adrenal tissue were obtained either by immediate autopsy in non-survivors or after euthanasia at 72-h for survivors. Vascular endothelium ultrastructure was evaluated by transmission electron microscopy (TEM) of ultra-thin tissue sections. Biological activity of EC was determined by light microscopy (LM) using a polyclonal antibody targeting von Willebrand Factor (vWF). Apoptosis was assessed, also in tissue sections, by deoxyuridine triphosphate nick end-labeling (TUNEL) procedure. Results: In heatstroke animals, there were marked EC changes in lungs, spleen, jejunum, kidneys and liver, demonstrated by TEM, as increased cytoplasmic membrane convolutions that included formation of villi projecting into the vessel lumina, and increase in the width of the gaps between ECs. Migration of neutrophils, platelets and erythrocytes through these widened gaps was noted. Weibel-Palade bodies were increased both in size and number in EC of jejunum, lungs and kidneys. This increase correlated with increased endothelial expression of immunologically detectable vWF. TEM also showed that there was increased apoptosis manifested by nuclear chromatin condensation and karyorrhexis and formation of cytoplasmic myelin whorls. Increased EC apoptosis was also observed by TUNEL in the jejunum, lungs, liver and spleen. All these changes were greater in animals with severe HS than in animals with moderate HS, whereas sham heated control animals showed no significant changes. Conclusion: Widespread EC injury with apoptotic cell death is consistent with the hypothesis that the endothelium may play a pathogenic role in heatstroke.

scholarly journals Global Transcriptional Analysis of Yeast Cell Death Induced by Mutation of Sister Chromatid Cohesin

2008 ◽  
Vol 2008 ◽  
pp. 1-16 ◽  
Author(s):  
Qun Ren ◽  
Hui Yang ◽  
Bifeng Gao ◽  
Zhaojie Zhang
Keyword(s):  
Cell Death ◽  
Stress Response ◽  
Internal Stress ◽  
Sister Chromatid ◽  
Apoptotic Cell ◽  
Chromatin Condensation ◽  
External Stress ◽  
Apoptotic Cell Death ◽  
Transcriptional Analysis ◽  
External Stimuli

Cohesin is a protein complex that regulates sister chromatid cohesin during cell division. Malfunction in chromatid cohesin results in chromosome missegregation and aneuploidy. Here, we report that mutations of MCD1 and PDS5, two major components of cohesin in budding yeast, cause apoptotic cell death, which is characterized by externalization of phosphatidylserine at cytoplasmic membrane, chromatin condensation and fragmentation, and ROS production. Microarray analysis suggests that the cell death caused by mutation of MCD1 or PDS5 is due to the internal stress response, contrasting to the environmental or external stress response induced by external stimuli, such as hydrogen peroxide. A common feature shared by the internal stress response and external stress response is the response to stimulus, including response to DNA damage, mitochondria functions, and oxidative stress, which play an important role in yeast apoptotic cell death.

ER stress related lipid accumulation and apoptotic cell death in nonalcoholic fatty liver diesease

2017 ◽  
Vol 108 ◽  
pp. S58
Author(s):  
Tugce Demirel ◽  
Erdi Sozen ◽  
Ali Sahin ◽  
Betul Karademir ◽  
Nesrin Kartal Ozer
Keyword(s):  
Cell Death ◽  
Fatty Liver ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Nonalcoholic Fatty Liver
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