Curcuma longa Linn extract suppresses neuronal apoptosis induction by sevoflurane via activation of the ERK1/2 pathway

Purpose: To investigate Curcuma longa Linn against neuronal damage induced by exposure to sevoflurane during surgical procedures. Methods: A sealed box made of transparent glass was used for anaesthetic exposure of neurons. The neurons were exposed to Curcuma longa Linn at doses of 1.5, 3, 6 and 12 μM prior to viability assessment using MTT assay. The effect of Curcuma longa Linn treatment on protein expression was determined using western blotting. Results: Sevoflurane exposure led to significant and time-dependent reductions in neuronal proliferation, when compared to unexposed cells (p < 0.05). Curcuma longa Linn at doses of 1.5, 3, 6 and 12 μM significantly decreased sevoflurane-mediated neuronal apoptosis. It reduced cleaved caspase-3 and Bax levels in neurons. However, the Curcuma longa Linn-mediated inhibition of sevoflurane-induced neuronal apoptosis was significantly suppressed by VPC23019 (p < 0.05). The p- ERK1/2 level was dose-dependently up-regulated in neurons exposed to sevoflurane on treatment with Curcuma longa Linn. Moreover, VPC23019 reversed the upregulatory effect of Curcuma longa Linn on p-ERK1/2 expression in sevoflurane-exposed neurons (p < 0.05). Conclusion: Curcuma longa Linn reversed sevoflurane-induced neuronal apoptosis by elevating p- ERK1/2 expression. Therefore, Curcuma longa Linn exerts inhibitory effect on anaesthesia-induced apoptosis in neurons, and may be useful for the treatment of this condition.

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Porphyra-334, a mycosporine-like amino acid, attenuates UV-induced apoptosis in HaCaT cells

Acta Pharmaceutica ◽

10.1515/acph-2017-0015 ◽

2017 ◽

Vol 67 (2) ◽

pp. 257-264 ◽

Cited By ~ 6

Author(s):

Sung-Suk Suh ◽

Se Kyung Oh ◽

Sung Gu Lee ◽

Il-Chan Kim ◽

Sanghee Kim

Keyword(s):

Caspase 3 ◽

Biological Activities ◽

Inhibitory Effect ◽

In Vitro Assays ◽

Control Group ◽

Hacat Cells ◽

Dramatic Decrease ◽

Induced Apoptosis ◽

Active Caspase

Abstract The main aim of the current research was to study the effect of porphyra-334, one of mycosporine-like amino acids (MAAs), well known as UV-absorbing compounds, on UVinduced apoptosis in human immortalized keratinocyte (HaCaT) cells. Due to their UV-screening capacity and ability to prevent UV-induced DNA damage, MAAs have recently attracted considerable attention in both industry and research in pharmacology. Herein, human HaCaT cells were used to determine the biological activities of porphyra- 334 by various in vitro assays, including proliferation, apoptosis and Western blot assays. The proliferation rate of UV-irradiated HaCaT cells was significantly decreased compared to the control group. Pretreatment with porphyra- 334 markedly attenuated the inhibitory effect of UV and induced a dramatic decrease in the apoptotic rate. Expression of active caspase-3 protein was increased in response to UV irradiation, while caspase-3 levels were similar between cells treated with porphyra-334 and the non-irradiated control group. Taken together, our data suggest that porphyra-334 inhibits UV-induced apoptosis in HaCaT cells through attenuation of the caspase pathway.

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Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cδ–dependent mechanisms

Blood ◽

10.1182/blood-2004-10-4011 ◽

2005 ◽

Vol 105 (9) ◽

pp. 3714-3721 ◽

Cited By ~ 40

Author(s):

Man-Gen Song ◽

Shen-Meng Gao ◽

Ke-Ming Du ◽

Min Xu ◽

Yun Yu ◽

...

Keyword(s):

Protein Kinase ◽

Caspase 3 ◽

Specific Inhibitor ◽

Leukemic Cell ◽

K562 Cells ◽

Early Event ◽

Apoptosis Induction ◽

Proteolytic Activation ◽

Induced Apoptosis ◽

Protein Kinase Cδ

AbstractAs a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. In the present study, we report that NSC606985, a rarely studied camptothecin analog, induces apoptosis in acute myeloid leukemia (AML) cells NB4 and U937 and inhibits the proliferation without cell death in breakpoint cluster region–Abelson murine leukemia (bcr-abl) kinase-carrying leukemic K562 cells. For apoptosis induction or growth arrest, nanomolar concentrations of NSC606985 are sufficient. At such low concentrations, this agent also significantly inhibits the clonogenic activity of hematopoietic progenitors from patients with AML. For apoptosis induction, NSC606985 rapidly induces the proteolytic activation of protein kinase Cδ (PKCδ) with loss of mitochondrial transmembrane potential (ΔΨm) and caspase-3 activation. Cotreatment with rottlerin, a PKCδ-specific inhibitor, completely blocks NSC606985-induced mitochondrial ΔΨm loss and caspase-3 activation, while the inhibition of caspase-3 by z-DEVD-fluoromethyl ketone (Z-DEVD-fmk) only partially attenuates PKCδ activation and apoptosis. These data indicate that NSC606985-induced PKCδ activation is an early event upstream to mitochondrial ΔΨm loss and caspase-3 activation, while activated caspase-3 has an amplifying effect on PKCδ proteolysis. In addition, NSC606985-induced apoptosis by PKCδ also involves caspase-3–independent mechanisms. Taken together, our results suggest that NSC606985 is a potential agent for the treatment of AML.

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NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion

AJP Cell Physiology ◽

10.1152/ajpcell.00480.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. C1009-C1018 ◽

Cited By ~ 67

Author(s):

Tongtong Zou ◽

Jaladanki N. Rao ◽

Xin Guo ◽

Lan Liu ◽

Huifang M. Zhang ◽

...

Keyword(s):

Epithelial Cells ◽

Caspase 3 ◽

Intestinal Epithelial Cells ◽

Specific Inhibitor ◽

Inhibitory Effect ◽

Intestinal Epithelial ◽

Tnf Α ◽

Induced Apoptosis ◽

Necrosis Factor ◽

Active Caspase

Apoptosis plays a crucial role in maintenance of intestinal epithelial integrity and is highly regulated by numerous factors, including cellular polyamines. We recently showed that polyamines regulate nuclear factor (NF)-κB activity in normal intestinal epithelial (IEC-6) cells and that polyamine depletion activates NF-κB and promotes resistance to apoptosis. The current study went further to determine whether the inhibitors of apoptosis (IAP) family of proteins, c-IAP2 and XIAP, are downstream targets of activated NF-κB and play a role in antiapoptotic activity of polyamine depletion in IEC-6 cells. Depletion of cellular polyamines by α-difluoromethylornithine not only activated NF-κB activity but also increased expression of c-IAP2 and XIAP. Specific inhibition of NF-κB by the recombinant adenoviral vector containing IκBα superrepressor (Ad Iκ BSR) prevented the induction of c-IAP2 and XIAP in polyamine-deficient cells. Decreased levels of c-IAP2 and XIAP proteins by inactivation of NF-κB through Ad Iκ BSR infection or treatment with the specific inhibitor Smac also overcame the resistance of polyamine-depleted cells to apoptosis induced by the combination of tumor necrosis factor (TNF)-α and cycloheximide (CHX). Although polyamine depletion did not alter levels of procaspase-3 protein, it inhibited formation of the active caspase-3. Decreased levels of c-IAP2 and XIAP by Smac prevented the inhibitory effect of polyamine depletion on the cleavage of procaspase-3 to the active caspase-3. These results indicate that polyamine depletion increases expression of c-IAP2 and XIAP by activating NF-κB in intestinal epithelial cells. Increased c-IAP2 and XIAP after polyamine depletion induce the resistance to TNF-α/CHX-induced apoptosis, at least partially, through inhibition of the caspase-3 activity.

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UV-Induced Apoptosis in Resistant HeLa Cells

Bioscience Reports ◽

10.1023/a:1005515400285 ◽

2000 ◽

Vol 20 (2) ◽

pp. 99-108 ◽

Cited By ~ 16

Author(s):

P. Kamarajan ◽

Chuck C.-K. Chao

Keyword(s):

Hela Cells ◽

Caspase 3 ◽

Chromatin Condensation ◽

Time Dependent ◽

Consistent Difference ◽

Dependent Manner ◽

Downstream Target ◽

Signaling Complex ◽

Induced Apoptosis ◽

Resistant Cells

Recently, apoptosis (genetically programmed cell death) induced by UV hasbeen documented in some cell culture models. However, the significance ofapoptosis in UV-induced cytotoxicity and resistance is uncertain. In thisstudy, we investigated the induction of apoptosis in HeLa cells and itsrole in acquired UV-resistance. The membrane receptor Fas was induced toassembly, and its immediate downstream target, caspase-8, was induced byUV in a dose- and time-dependent manner. Caspase-10, another possiblecandidate for forming the death-inducing signaling complex with Fas, wasalso activated in a dose- and time-dependent manner. There was significantactivation of caspase 9, 3 and 2 by UV. The apoptotic pathways appeared tobe normal in acquired UV-resistant HeLa cells. In addition, there was a UVdose-dependent induction of chromatin condensation in both parental andUV-resistant cells. However, resistant cells displayed significant reductionin chromatin condensation at lower doses. Inhibition of caspase-3 activation byspecific inhibitor significantly reduced the chromatin condensation in bothcell types, and unexpectedly, the difference between the two cell lines wascompletely eradicated, suggesting that the caspase-3 pathway plays asignificant role in reducing apoptosis in resistant cells. The resultsindicate that UV induces apoptosis by direct activation of apoptoticproteins in HeLa and resistant cells. Although resistant cells displayedpartial inhibition of UV-induced apoptosis through the caspase-3 pathway,there was no consistent difference in the activation of this and relatedcaspase-9 caspases compared to parental HeLa cells.

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12-Epi-Napelline Inhibits Leukemia Cell Proliferation via the PI3K/AKT Signaling Pathway In Vitro and In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6687519 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Jia Han ◽

Wei Hou ◽

Bi-qing Cai ◽

Fan Zhang ◽

Jian-cai Tang

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Caspase 3 ◽

Animal Experiments ◽

Leukemia Cell ◽

Tumor Model ◽

Inhibitory Effect ◽

Induced Apoptosis

This study aimed to investigate the inhibitory effect of 12-epi-napelline on leukemia cells and its possible mechanisms. The inhibitory effects of 12-epi-napelline on K-562 and HL-60 cells were evaluated using the CCK-8 assay, cell cycle arrest and apoptosis were detected by flow cytometry, and the expression of related proteins was measured by western blot. A K-562 tumor model was established to evaluate the antitumor effect of 12-epi-napelline in vivo. A reduction in leukemia cell viability was observed after treatment with 12-epi-napelline. It was determined that the cell cycle was arrested in the G0/G1 phase, and the cell apoptosis rate was increased. Moreover, caspase-3 and Bcl-2 were downregulated, whereas cleaved caspase-3 and caspase-9 were upregulated. Further study revealed that 12-epi-napelline could suppress the expression of PI3K, AKT, p-AKT, and mTOR. Insulin-like growth factor 1 (IGF-1) attenuated 12-epi-napelline-induced apoptosis and ameliorated the repression of PI3K, AKT, p-AKT, and mTOR by 12-epi-napelline. Animal experiments clearly showed that 12-epi-napelline inhibited tumor growth. In conclusion, 12-epi-napelline restrained leukemia cell proliferation by suppressing the PI3K/AKT/mTOR pathway in vitro and in vivo.

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A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells

International Journal of Molecular Sciences ◽

10.3390/ijms221910195 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10195

Author(s):

Sagrario Martin-Aragon ◽

Paloma Bermejo-Bescós ◽

Juana Benedí ◽

Carlos Raposo ◽

Franklim Marques ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Caspase 3 ◽

Neuronal Damage ◽

Dairy Product ◽

Preliminary Evidence ◽

Bovine Colostrum ◽

Osteoblastic Cells ◽

Osteoblastic Cell ◽

Induced Apoptosis

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

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Smac Mimetic-Mediated Sensitization Of Childhood ALL Cells For Drug-Induced Apoptosis Independent Of TNFα and NFκB Signaling Pathways

Blood ◽

10.1182/blood.v122.21.2911.2911 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2911-2911

Author(s):

Karin Schmelz ◽

Nina Weichert ◽

Jutta Proba ◽

Marie-Sophie Erdmann ◽

Patrick Hundsdoerfer

Keyword(s):

Signaling Pathways ◽

Tumor Cells ◽

Caspase 3 ◽

Caspase 8 ◽

Apoptosis Induction ◽

Caspase 9 ◽

Drug Induced ◽

Childhood All ◽

Apoptosis Pathway ◽

Induced Apoptosis

Abstract Targeting inhibitor of apoptosis proteins (IAPs) using small molecular Smac mimetics (SM) has been shown to offer a novel promising treatment strategy for resistant malignant diseases including childhood acute lymphoblastic leukemia (ALL). The effect of SM alone has been shown to be associated with endogenous TNFα expression, therefore tumor cells can be classified into sensitive or resistant against apoptosis induction by SM alone. In SM sensitive tumor cells the effect of SM has been shown to be mediated mainly by degradation of cellular IAP (cIAP) and activation of TNFα and NFκB signaling pathways but not inhibition of XIAP. We show here, that sensitivity of ALL cells to SM alone (as well as TNFα expression) is highly variable. Nevertheless even in ALL cells resistant against SM alone, treatment with SM resulted in significant sensitization for drugs used within standard induction therapy for childhood ALL. Sensitization for drug-induced apoptosis by SM was not only mediated by activation of the intrinsic (cleavage of caspase 9) but also extrinsic apoptosis pathway (cleavage of caspase 8). Surprisingly, SM-induced cIAP degradation alone was not sufficient for caspase 8 activation and apoptosis induction. Consistently, SM-mediated sensitization for drug-induced apoptosis was independent of TNFα and NFκB signaling pathways. We demonstrate that caspase 8 activation by combined treatment with SM and cytostatic drugs is blocked by inhibition of caspase 3 and caspase 9 and therefore occurs downstream of intrinsic apoptosis pathway activation. In conclusion, our data argue for a model comprising inhibition of XIAP-mediated blockade of caspase 3/9 as the central effect of SM in chemo-sensitization of childhood ALL cells resistant against SM-alone. Disclosures: No relevant conflicts of interest to declare.

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Apoptosis and Caspase 3 Pathway Role on Anti-Proliferative Effects of Scrophulariaoxy Sepala Methanolic Extract on Caco-2 Cells

Drug Research ◽

10.1055/s-0043-110483 ◽

2017 ◽

Vol 67 (09) ◽

pp. 547-552 ◽

Cited By ~ 1

Author(s):

Ali Namvaran ◽

Mehdi Fazeli ◽

Safar Farajnia ◽

Gholamreza Hamidian ◽

Hassan Rezazadeh

Keyword(s):

Caspase 3 ◽

Methanolic Extract ◽

Inhibitory Effect ◽

Control Group ◽

Common Source ◽

Dependent Manner ◽

High Doses ◽

New Treatment ◽

Induced Apoptosis ◽

Chemotherapy Agents

AbstractColorectal cancer is one the most important malignancies worldwide and finding new treatment option for this cancer is of high priority. Natural compounds are common source of drugs for treatment of various diseases including cancers. The aim of this study was to investigate the effects of Scrophularia oxysepala extract on Caco-2 cells and explore the possible role of caspase 3 pathway in inducing cell death in this cancer cells in compare with chemotherapy agents of cisplatin and capecitabine. The methanolic extract of Scrophularia oxysepala (SO) was prepared by drench method. The IC50 of extract, cisplatin and capecitabine on Caco-2 cells were determined by MTT assay. The effect of SO extract on caspase 3 expression and inducing apoptosis were determined using TUNEL assay and caspase 3 ELISA methods, respectively. The IC50 of SO extract, cisplatin and capecitabine were 300, 195 and 80 µg/ml, respectively. Analysis for apoptosis revealed that SO methanolic extract increased apoptosis significantly (P<0.001) compared with control group. The effect of high doses of SO extract on apoptosis induction were comparable to cisplatin but significantly were higher than capecitabine. Only high doses of SO methanolic extract showed significant effects (P<0.05) on increasing caspase 3 compared to control group. The methanolic extract of SO showed inhibitory effect on Caco-2 cells and induced apoptosis in a dose-dependent manner comparable to cisplatin and higher than capecitabine 2 commonly used chemotherapeutic agent for various cancers.

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Peroxynitrite induces apoptosis of HL-60 cells by activation of a caspase-3 family protease

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.4.c855 ◽

1998 ◽

Vol 274 (4) ◽

pp. C855-C860 ◽

Cited By ~ 73

Author(s):

King-Teh Lin ◽

Ji-Yan Xue ◽

Marie C. Lin ◽

Eric G. Spokas ◽

Frank F. Sun ◽

...

Keyword(s):

Caspase 3 ◽

Specific Inhibitor ◽

Time Dependent ◽

Dependent Manner ◽

Active Process ◽

Fluorogenic Substrate ◽

Biological Product ◽

Caspase Family ◽

Protease Activation ◽

Induced Apoptosis

Apoptosis is an active process critical for the homeostasis of organisms. Enzymes of the caspase family are responsible for executing this process. We have previously shown that peroxynitrite (ONOO−), a biological product generated from the interaction of nitric oxide and superoxide, induces apoptosis of HL-60 cells. The aim of this study was to elucidate the mechanisms involved in the execution process of peroxynitrite-induced apoptosis. Proteolytic cleavage of poly(ADP-ribose) polymerase, an indication of caspase-3 family protease activation and an early biochemical event accompanying apoptosis, was observed in a time-dependent manner during peroxynitrite-induced apoptosis of HL-60 cells. Activation of caspase-3 during peroxynitrite-induced apoptosis was substantiated by monitoring proteolysis of the caspase-3 proenzyme and by measuring caspase-3 activity with a fluorogenic substrate. Furthermore, pretreatment of HL-60 cells with N-acetyl-Asp-Glu-Val-Asp-aldehyde, a specific inhibitor of caspase-3, but not N-acetyl-Tyr-Val-Ala-Asp-aldehyde, a specific inhibitor of caspase-1, decreased peroxynitrite-induced apoptosis. These results suggest that the activation of a caspase-3 family protease is essential for initiating the execution process of peroxynitrite-induced apoptosis of HL-60 cells.

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Severibuxine, Isolated from Severinia buxifolia, Induces Apoptosis in HL-60 Leukemia Cells

Natural Product Communications ◽

10.1177/1934578x1300800623 ◽

2013 ◽

Vol 8 (6) ◽

pp. 1934578X1300800

Author(s):

Chihiro Ito ◽

Tomiyasu Murata ◽

Midori Kato ◽

Natsu Suzuki ◽

Tian-Shung Wu ◽

...

Keyword(s):

Caspase 3 ◽

Microscopic Analysis ◽

Time Dependent ◽

Root Bark ◽

Dependent Manner ◽

Caspase 9 ◽

Nuclear Condensation ◽

Apoptotic Effect ◽

Induced Apoptosis ◽

Severinia Buxifolia

In an ongoing search for cancer-preventing compounds derived from plant sources, we isolated the quinolin-2,4-dione alkaloid severibuxine from the root bark of Severinia buxifolia collected in Taiwan and then examined the apoptotic effect of this compound. Severibuxine showed cytotoxicity to leukemia HL-60 cells (IC50 = 12.3±0.6 μM). Fluorescence microscopic analysis of cells stained with Hoechst 33342 indicated that the percentage of apoptotic cells showing nuclear condensation and fragmentation increased in a time-dependent manner. In addition, the activities of caspase-9 and caspase-3 were also enhanced in a time-dependent manner upon treatment with severibuxine. The addition of caspase-9 and caspase-3 inhibitors blocked severibuxine-mediated apoptosis. Upon treatment with severibuxine, the mitochondrial membrane potential decreased in a time-dependent manner. Severibuxine induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.

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