Association of the apoptotic effect of the coffee deterpene kahweol on human colon cancer cell with the expression of heat shock proteins (HSPs).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 622-622
Author(s):  
Sung Chul Park ◽  
Dong Wook Choi ◽  
Jin Myung Park ◽  
Dae Hee Choi ◽  
Chang Don Kang ◽  
...  
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Caspase 3 ◽  
Human Colon ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Apoptotic Effect ◽  
Ldh Assay ◽  
Shock Proteins ◽  
Ht 29

622 Background: It has been reported that coffee has a preventative effect in several cancers because of its anti-oxidant, anti-inflammatory, and anti-tumor properties. However, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis, and poor response to chemotherapy. Methods: We investigated the apoptotic effect of major components of coffee in the HT-29 human colon adenocarcinoma cells and evaluated the antitumor mechanism via the regulation of HSPs expression. HT-29 cells were cultured with bioactive compounds of coffee such as caffeine, chlorogenic acid, caffeic acid, and kahweol. Cell viability was determined by MTT and LDH assay according to the concentration of each component. Western blot assay was taken for evaluation of the apoptosis-related signals such as cleaved caspase-3, cleaved PAPR, Bcl-2, phospho-AKT(p-AKT), and HSPs including HSP40, HSP70, and HSP90. Results: Among the various coffee compounds, only kahweol showed significant anti-tumor cell activity, and cell death was observed in a concentration-dependent manner on MTT and LDH assay. Kahweol induced an increase in expression of cleaved caspase-3 and PAPR. In contrast, the reduction of anti-apoptotic proteins such as Bcl-2 and p-AKT was derived. HSPs including HSP40, HSP70, and HSP90 were decreased by kahweol treatment. HSP70 inhibitor such as quercetin and triptolide showed the significantly decreased viability of HT-29 cells. Conclusions: Kahweol had a cytotoxic effect on HT-29 cells via the apoptotic signal pathway in a concentration-dependent manner and inhibited the expressions of HSPs. HSP70 inhibitors showed tumor cell cytotoxicity, suggesting that HSP might play a significant role in the proliferation of cancer cells.

scholarly journals Anticancer effects of mifepristone on human uveal melanoma cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Prisca Bustamante Alvarez ◽  
Alexander Laskaris ◽  
Alicia A. Goyeneche ◽  
Yunxi Chen ◽  
Carlos M. Telleria ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Progesterone Receptor ◽  
Dna Fragmentation ◽  
Cell Lines ◽  
Caspase 3 ◽  
Annexin V ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Free Dna

Abstract Background Uveal melanoma (UM), the most prevalent intraocular tumor in adults, is a highly metastatic and drug resistant lesion. Recent studies have demonstrated cytotoxic and anti-metastatic effects of the antiprogestin and antiglucocorticoid mifepristone (MF) in vitro and in clinical trials involving meningioma, colon, breast, and ovarian cancers. Drug repurposing is a cost-effective approach to bring approved drugs with good safety profiles to the clinic. This current study assessed the cytotoxic effects of MF in human UM cell lines of different genetic backgrounds. Methods The effects of incremental concentrations of MF (0, 5, 10, 20, or 40 μM) on a panel of human UM primary (MEL270, 92.1, MP41, and MP46) and metastatic (OMM2.5) cells were evaluated. Cells were incubated with MF for up to 72 h before subsequent assays were conducted. Cellular functionality and viability were assessed by Cell Counting Kit-8, trypan blue exclusion assay, and quantitative label-free IncuCyte live-cell analysis. Cell death was analyzed by binding of Annexin V-FITC and/or PI, caspase-3/7 activity, and DNA fragmentation. Additionally, the release of cell-free DNA was assessed by droplet digital PCR, while the expression of progesterone and glucocorticoid receptors was determined by quantitative real-time reverse transcriptase PCR. Results MF treatment reduced cellular proliferation and viability of all UM cell lines studied in a concentration-dependent manner. A reduction in cell growth was observed at lower concentrations of MF, with evidence of cell death at higher concentrations. A significant increase in Annexin V-FITC and PI double positive cells, caspase-3/7 activity, DNA fragmentation, and cell-free DNA release suggests potent cytotoxicity of MF. None of the tested human UM cells expressed the classical progesterone receptor in the absence or presence of MF treatment, suggesting a mechanism independent of the modulation of the cognate nuclear progesterone receptor. In turn, all cells expressed non-classical progesterone receptors and the glucocorticoid receptor. Conclusion This study demonstrates that MF impedes the proliferation of UM cells in a concentration-dependent manner. We report that MF treatment at lower concentrations results in cell growth arrest, while increasing the concentration leads to lethality. MF, which has a good safety profile, could be a reliable adjuvant of a repurposing therapy against UM.

scholarly journals Cytoprotective Activity ofGlycyrrhizae radixExtract against Arsenite-Induced Cytotoxicity

2008 ◽  
Vol 5 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Sang Chan Kim ◽  
Sook Jahr Park ◽  
Jong Rok Lee ◽  
Jung Cheol Seo ◽  
Chae Ha Yang ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Herbal Medicines ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cytoprotective Activity ◽  
Flow Cytometric ◽  
H4iie Cells ◽  
Cell Line Cell

Licorice,Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml−1) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3.

Haeamtang Induces Apoptosis of Colon Cancer HT-29 Cells through Activation of Caspase-3

2007 ◽  
Vol 35 (05) ◽  
pp. 897-909 ◽  
Author(s):  
Phil-Dong Moon ◽  
Hyun-Na Koo ◽  
Hyun-Ja Jeong ◽  
Ho-Jeong Na ◽  
Su-Jin Kim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Flow Cytometry ◽  
Cell Death ◽  
Mtt Assay ◽  
Caspase 3 ◽  
Water Extract ◽  
Time Dependent ◽  
Dependent Manner ◽  
Caspase Inhibitor ◽  
Ht 29

The effect of Haeamtang (HAT) on the colon cancer HT-29 cells was investigated in this study. A water extract of HAT significantly decreased the number of HT-29 cells in a dose-and time-dependent manner as determined by a MTT assay. Flow cytometry results revealed a dose- and time-dependent increase of dead cells in HT-29 cells treated with HAT extract. The anticancer activity of the H AT extract is attributed to apoptosis induced in HT-29 cells, which was demonstrated by increased caspase-3 activity and poly-ADP-ribose polymerase fragmentation. A selective caspase inhibitor, z-VAD-fmk, inhibited the HAT-induced cell death. Taken together, these results demonstrate that HAT extract induces apoptosis in HT-29 cells.

scholarly journals Quercetin Induces Mitochondrial Mediated Apoptosis and Protective Autophagy in Human Glioblastoma U373MG Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hyeonji Kim ◽  
Jeong Yong Moon ◽  
Kwang Seok Ahn ◽  
Somi Kim Cho
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Concentration Dependent Manner ◽  
Proteolytic Activation ◽  
Caspase 7 ◽  
Dietary Flavonoid ◽  
Malignant Glioma Cells

Quercetin is a dietary flavonoid with known antitumor effects against several types of cancers by promoting apoptotic cell death and inducing cell cycle arrest. However, U373MG malignant glioma cells expressing mutant p53 are resistant to a 24 h quercetin treatment. In this study, the anticancer effect of quercetin was reevaluated in U373MG cells, and quercetin was found to be significantly effective in inhibiting proliferation of U373MG cells in a concentration-dependent manner after 48 and 72 h of incubation. Quercetin induced U373MG cell death through apoptosis, as evidenced by the increased number of cells in the sub-G1 phase, the appearance of fragmented nuclei, decreased mitochondrial membrane potential, proteolytic activation of caspase-3 and caspase-7, an increase in caspase-3 and 9 activities, and degradation of poly(ADP-ribose) polymerase protein. Furthermore, quercetin activated JNK and increased the expression of p53, which translocated to the mitochondria and simultaneously led to the release of cytochrome c from mitochondria to the cytosol. We also found that quercetin induced autophagy. Pretreatment with chloroquine, an autophagy inhibitor, strongly augmented apoptosis in U373MG cells, indicating that quercetin induced protective autopagy in U373MG cells.

scholarly journals Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

2021 ◽  
Vol 22 (13) ◽  
pp. 6785
Author(s):  
Valeria Sogos ◽  
Paola Caria ◽  
Clara Porcedda ◽  
Rafaela Mostallino ◽  
Franca Piras ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Concentration Dependent Manner ◽  
Mechanisms Of Toxicity ◽  
Neuronal Cell Lines

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

Progesterone enhances target gene transcription by receptor free of heat shock proteins hsp90, hsp56, and hsp70

1991 ◽  
Vol 11 (10) ◽  
pp. 4998-5004
Author(s):  
M K Bagchi ◽  
S Y Tsai ◽  
M J Tsai ◽  
B W O'Malley
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Transcriptional Activation ◽  
Target Gene ◽  
Steroid Hormone ◽  
Receptor Activation ◽  
Target Cells ◽  
Dependent Manner ◽  
Shock Proteins

Steroid receptors regulate transcription of target genes in vivo and in vitro in a steroid hormone-dependent manner. Unoccupied progesterone receptor exists in the low-salt homogenates of target cells as a functionally inactive 8 to 10S complex with several nonreceptor components such as two molecules of 90-kDa heat shock protein (hsp90), a 70-kDa heat shock protein (hsp70), and a 56-kDa heat shock protein (hsp56). Ligand-induced dissociation of receptor-associated proteins such as hsp90 has been proposed as the mechanism of receptor activation. Nevertheless, it has not been established whether, beyond release of heat shock proteins, the steroidal ligand plays a role in modulating receptor activity. To examine whether the release of these nonreceptor proteins from receptor complex results in a constitutively active receptor, we isolated an unliganded receptor form essentially free of hsp90, hsp70, and hsp56. Using a recently developed steroid hormone-responsive cell-free transcription system, we demonstrate for the first time that the dissociation of heat shock proteins is not sufficient to generate a functionally active receptor. This purified receptor still requires hormone for high-affinity binding to a progesterone response element and for efficient transcriptional activation of a target gene. When an antiprogestin, Ru486, is bound to the receptor, it fails to promote efficient transcription. We propose that in the cell, in addition to the release of receptor-associated inhibitory proteins, a distinct hormone-mediated activation event must precede efficient gene activation.

Garcinol exhibits anti-proliferative activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells

2016 ◽  
Vol 36 (7) ◽  
pp. 692-700 ◽  
Author(s):  
T Ranjbarnejad ◽  
M Saidijam ◽  
M sadat tafakh ◽  
M Pourjafar ◽  
F Talebzadeh ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Matrix Metalloproteinase ◽  
Caspase 3 ◽  
Human Colon ◽  
Prostaglandin E ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Prostaglandin E Synthase ◽  
Human Colon Cancer Cells ◽  
Ht 29

Background: Colorectal cancer is the fourth leading cause of death. Various natural compounds are known to have antitumor properties. Garcinol, a polyisoprenylated benzophenone, has antioxidant and anti-inflammatory properties. In the current study, we investigated the anticancer activity of garcinol on human colorectal adenocarcinoma cell line (HT-29) human colon cancer cells. Methods: HT-29 cells were treated with various concentrations of garcinol for 24 h. The effect of garcinol on HT-29 cells proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; the mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were examined by quantitative real-time polymerase chain reaction; apoptosis was detected by proportion of sub-G1 cell; caspase 3 activity and prostaglandin E2 (PGE2) level were determined by enzyme-linked immunosorbent assay and HT-29 cells migration was assessed using scratch test. Results: Garcinol preconditioning markedly decreased the expression of mPGES-1, HIF-1α, VEGF, CXCR4, MMP-2, and MMP-9. The proportion of cells in sub-G1 phase and caspase 3 activity were increased by garcinol treatment whereas the cell proliferation, PGE2 level, and cell migration were decreased in these cells, compared to the control group. Conclusion: Our findings suggest that garcinol plays a critical role in elevating apoptosis and inhibiting HT-29 cells proliferation, angiogenesis, and invasion by suppressing the mPGES-1/PGE2/HIF-1α signaling pathways.

scholarly journals In situ localization of heat-shock proteins and cell death labelling in the salivary gland of acaricide-treated honeybee larvae

Apidologie ◽  
2006 ◽  
Vol 37 (5) ◽  
pp. 507-516 ◽  
Author(s):  
Elaine C.M. Silva-Zacarin ◽  
Ales Gregorc ◽  
Regina L.M. Silva de Moraes
Keyword(s):  
Cell Death ◽  
Salivary Gland ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Shock Proteins

scholarly journals Immunomodulation of function of small heat shock proteins prevents their assembly into heat stress granules and results in cell death at sublethal temperatures

2004 ◽  
Vol 41 (2) ◽  
pp. 269-281 ◽  
Author(s):  
Sergey Miroshnichenko ◽  
Joanna Tripp ◽  
Uta zur Nieden ◽  
Dieter Neumann ◽  
Udo Conrad ◽  
...  
Keyword(s):  
Cell Death ◽  
Heat Stress ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Stress Granules ◽  
Small Heat Shock Proteins ◽  
Shock Proteins

scholarly journals Minocycline reduces inflammatory response and cell death in a S100B retina degeneration model

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Pia Grotegut ◽  
Natarajan Perumal ◽  
Sandra Kuehn ◽  
Andreas Smit ◽  
H. Burkhard Dick ◽  
...  
Keyword(s):  
Cell Death ◽  
Body Weight ◽  
Optic Nerve ◽  
Inflammatory Response ◽  
Negative Impact ◽  
Dependent Manner ◽  
Label Free ◽  
Proteomics Analysis ◽  
Concentration Dependent Manner ◽  
Minocycline Treatment

Abstract Background Previous studies noted that intravitreal injection of S100B triggered a glaucoma-like degeneration of retina and optic nerve as well as microglia activation after 14 days. The precise role of microglia in our intravitreal S100B model is still unclear. Hence, microglia were inhibited through minocycline. The aim is to investigate whether microglia have a significant influence on the degeneration process or whether they are only a side effect in the model studied here. Methods Minocycline was applied daily in rats by intraperitoneal injection using two different concentrations (13.5 mg/kg body weight, 25 mg/kg body weight). One day after treatment start, S100B or PBS was intravitreally injected in one eye per rat. The naïve groups received no injections. This resulted in a total of five groups (naïve n = 14, PBS n = 14, S100B n = 13, 13.5 mg/kg mino n = 15, 25 mg/kg mino n = 15). At day 14, electroretinogram measurements were performed, followed by immunofluorescence and label-free quantitative proteomics analysis. The focus of these investigations was on the survival of RGCs as well as their axons, the response of the microglia, and the identification of further pathological modes of action of S100B. Results The best signal transmission was detected via ERG in the 13.5 mg/kg mino group. The inhibition of the microglia protected optic nerve neurofilaments and decreased the negative impact of S100B on RGCs. However, the minocycline treatment could not trigger complete protection of RGCs. Furthermore, in retina and optic nerve, the minocycline treatment reduced the number and activity of S100B-triggered microglia in a concentration-dependent manner. Proteomics analysis showed that S100B application led to numerous metabolic functions and cellular stress, mainly an increased inflammatory response, glycolysis, and mitochondrial dysfunction, which caused oxidative stress in the retina. Importantly, the protective capability of lower dose of minocycline was unraveled by suppressing the apoptotic, inflammatory, and the altered metabolic processes caused by S100B insult in the retina. Conclusion Intravitreally injected S100B not only led to a pro-inflammatory microglial reaction, but also a mitochondrial and metabolic dysfunction. Also, these results suggest that an excessive microglial response may be a significant degenerative factor, but not the only trigger for increased cell death.

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