Enhanced in vitro photocytotoxicity of water-soluble dendritic pheophorbide-a

2015 ◽  
Vol 19 (07) ◽  
pp. 830-837 ◽  
Author(s):  
Eun Ji Lee ◽  
Hyoung Jun Kong ◽  
Young-Jin Kim ◽  
Jong S. Park ◽  
Myung-Seok Choi
Keyword(s):  
Aqueous Solution ◽  
Cell Death ◽  
Singlet Oxygen ◽  
Death Rate ◽  
Water Soluble ◽  
Pheophorbide A ◽  
Absorption Bands ◽  
Cell Death Rate ◽  
A Cell

Photosensitizers can produce highly reactive singlet oxygen with exposure to visible light and are used in photodynamic therapy to treat a variety of tumors. We report on the synthesis of triethylene glycol dendron-conjugated pheophorbide-a5, a novel photosensitizer. The characteristic absorption bands (Soret and Q-bands, λmax = 405 and 670 nm, respectively) of 5 were appeared clearly in aqueous solution, due to the improved water-solubility of the dendron moiety. The value of singlet oxygen quantum yield of 5 (ΦΔ = 0.22) was higher than free pheophorbide-a (ΦΔ = 0.17) as reference in aqueous solution. Compound 5 also exhibited an enhanced in vitro phototoxicity than pheophorbide-a (PhA) in the concentration range of 1.0–5.0 μg/mL: cell viability in cells treated with 5 was reduced by ~20%, indicating a cell death rate of ~80%, while PhA treatment resulted in a cell death rate of only about 10%. These results indicate that 5 will likely be more efficient in PDT applications. Compared with free PhA, compound 5 showed highly enhanced singlet oxygen generation ability and in vitro photocytotoxicity.

Increased cell death in osteopontin-deficient cardiac fibroblasts occurs by a caspase-3-independent pathway

2004 ◽  
Vol 287 (4) ◽  
pp. H1730-H1739 ◽  
Author(s):  
Ron Zohar ◽  
Baoqian Zhu ◽  
Peter Liu ◽  
Jaro Sodek ◽  
C. A. McCulloch
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Cardiac Fibroblasts ◽  
Chromatin Condensation ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Wild Type ◽  
Nuclear Fragmentation ◽  
A Cell

Reperfusion-induced oxidative injury to the myocardium promotes activation and proliferation of cardiac fibroblasts and repair by scar formation. Osteopontin (OPN) is a proinflammatory cytokine that is upregulated after reperfusion. To determine whether OPN enhances fibroblast survival after exposure to oxidants, cardiac fibroblasts from wild-type (WT) or OPN-null (OPN−/−) mice were treated in vitro with H2O2to model reperfusion injury. Within 1 h, membrane permeability to propidium iodide (PI) was increased from 5 to 60% in OPN−/−cells but was increased to only 20% in WT cells. In contrast, after 1–8 h of treatment with H2O2, the percent of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-stained cells was more than twofold higher in WT than OPN−/−cells. Electron microscopy of WT cells treated with H2O2showed chromatin condensation, nuclear fragmentation, and cytoplasmic and nuclear shrinkage, which are consistent with apoptosis. In contrast, H2O2-treated OPN−/−cardiac fibroblasts exhibited cell and nuclear swelling and membrane disruption that are indicative of cell necrosis. Treatment of OPN−/−and WT cells with a cell-permeable caspase-3 inhibitor reduced the percentage of TUNEL staining by more than fourfold in WT cells but decreased staining in OPN−/−cells by ∼30%. Although the percentage of PI-permeable WT cells was reduced threefold, the percent of PI-permeable OPN−/−cells was not altered. Restoration of OPN expression in OPN−/−fibroblasts reduced the percentage of PI-permeable cells but not TUNEL staining after H2O2treatment. Thus H2O2-induced cell death in OPN-deficient cardiac fibroblasts is mediated by a caspase-3-independent, necrotic pathway. We suggest that the increased expression of OPN in the myocardium after reperfusion may promote fibrosis by protecting cardiac fibroblasts from cell death.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

scholarly journals Comparison of organics and heavy metals acute toxicities to Vibrio fischeri

2016 ◽  
Vol 81 (6) ◽  
pp. 697-705 ◽  
Author(s):  
Xuepeng Yang ◽  
Yan Ji ◽  
Fangfang Wang ◽  
Jia Xu ◽  
Xiangzhen Liu ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Cell Death ◽  
Benzoic Acid ◽  
Death Rate ◽  
Vibrio Fischeri ◽  
Reaction Times ◽  
Inhibition Rate ◽  
Cell Death Rate ◽  
Bioluminescence Inhibition ◽  
The Difference

Vibrio fischeri bioluminescence inhibition has been widely used to test acute toxicities of metals and organics contaminants. However, the differences of metals and organics acute toxicities to V. fischeri have not been compared. Here, four heavy metals (Zn2+, Cu2+, Cd2+, Cr6+) and five organics (phenol, benzoic acid, p-hydroxy benzoic acid, nitro-benzene and benzene) acute toxicities to V. fischeri were investigated. Heavy metals toxicities to V. fischeri were increased along with the reaction time, while the organics toxicities kept the same level in different reaction times. In order to explain the difference, the relative cell death rate of V. fischeri was detected. In metals toxicities tests, the bioluminescence inhibition rate of V. fischeri was found to be significantly higher than the relative cell death rate (P<0.05), while for the organics toxicities tests, the cell death rate was similar to the bioluminescence inhibition rate. These results indicated that organics acute toxicities to V. fischeri could reflect the death of cell, but metals acute toxicities to V. fischeri may not lead to the death of cell, just represent the bioluminescence inhibition.

scholarly journals Antioxidant supplementation decreases the cell death rate in the prostatic stromal tissue of long-term castrated rats

2012 ◽  
Vol 38 (3) ◽  
pp. 419-425 ◽  
Author(s):  
Guilherme Fartes ◽  
Fábio Lorenzetti ◽  
Larissa Beloti Salvador ◽  
Valdemar Ortiz ◽  
Miriam Dambros
Keyword(s):  
Cell Death ◽  
Death Rate ◽  
Antioxidant Supplementation ◽  
Cell Death Rate ◽  
Stromal Tissue

scholarly journals Mortalin (GRP75/HSPA9) Promotes Survival and Proliferation of Thyroid Carcinoma Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 2069 ◽  
Author(s):  
Dmytro Starenki ◽  
Nadiya Sosonkina ◽  
Seung-Keun Hong ◽  
Ricardo V. Lloyd ◽  
Jong-In Park
Keyword(s):  
Cell Death ◽  
Thyroid Carcinoma ◽  
Thyroid Tumor ◽  
Anaplastic Thyroid Carcinoma ◽  
Mitochondrial Activity ◽  
Phase Arrest ◽  
M Phase ◽  
A Cell ◽  
Mitochondrial Hsp70

We previously reported that upregulation of mortalin (HSPA9/GRP75), the mitochondrial HSP70 chaperone, facilitates tumor cell proliferation and survival in human medullary thyroid carcinoma (MTC), proposing mortalin as a novel therapeutic target for MTC. In this report, we show that mortalin is also upregulated in other thyroid tumor types, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and anaplastic thyroid carcinoma (ATC), and that mortalin depletion can effectively induce growth arrest and cell death in human PTC (TPC-1), FTC (FTC133), and ATC (8505C and C643) cells in culture. Intriguingly, mortalin depletion induced varied effects on cell cycle arrest (G0/G1 phase arrest in TPC-1 and C643, G2/M phase arrest in 8505C, and mild G2/M phase arrest with increased sub-G0/G1 population in FTC133) and on the levels of TP53, E2F-1, p21CIP1, p27KIP1, and poly (ADP-ribose) polymerase cleavage in these cells, suggesting that thyroid tumor cells respond to mortalin depletion in a cell type-specific manner. In these cells, we also determined the efficacy of triphenyl-phosphonium-carboxy-proxyl (Mito-CP) because this mitochondria-targeted metabolism interfering agent exhibited similar tumor suppressive effects as mortalin depletion in MTC cells. Indeed, Mito-CP also induced robust caspase-dependent apoptosis in PTC and ATC cell lines in vitro, exhibiting IC50 lower than PLX4032 in 8505C cells and IC50 lower than vandetanib and cabozantinib in TPC-1 cells. Intriguingly, Mito-CP-induced cell death was partially rescued by mortalin overexpression, suggesting that Mito-CP may inactivate a mechanism that requires mortalin function. These findings support the significance of mortalin and mitochondrial activity in a broad spectrum of thyroid cancer.

In vitro assay of singlet oxygen generation in the presence of water-soluble derivatives of C60

Carbon ◽  
2004 ◽  
Vol 42 (5-6) ◽  
pp. 1195-1198 ◽  
Author(s):  
Bertrand Vileno ◽  
Andrzej Sienkiewicz ◽  
Małgorzata Lekka ◽  
Andrzej J. Kulik ◽  
László Forró
Keyword(s):  
Singlet Oxygen ◽  
In Vitro Assay ◽  
Water Soluble ◽  
Vitro Assay ◽  
Oxygen Generation ◽  
Singlet Oxygen Generation ◽  
Derivatives Of

New in vitro insights on a cell death pathway induced by magnolol and honokiol in aristolochic acid tubulotoxicity

2016 ◽  
Vol 87 ◽  
pp. 77-87 ◽  
Author(s):  
Valérian Bunel ◽  
Marie-Hélène Antoine ◽  
Caroline Stévigny ◽  
Joëlle Nortier ◽  
Pierre Duez
Keyword(s):  
Cell Death ◽  
Aristolochic Acid ◽  
Cell Death Pathway ◽  
A Cell

scholarly journals Towards Understanding the Involvement of H+-ATPase in Programmed Cell Death of Psammosilene tunicoides after Oxalic Acid Application

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6957
Author(s):  
Xinyu Jiang ◽  
Mohammad Aqa Mohammadi ◽  
Yuan Qin ◽  
Zongshen Zhang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Oxalic Acid ◽  
Atpase Activity ◽  
Intracellular Ph ◽  
Death Rate ◽  
Ph Value ◽  
Intracellular Acidification ◽  
Cell Death Rate

Psammosilene tunicoides is a unique perennial medicinal plant species native to the Southwestern regions of China. Its wild population is rare and endangered due to over-excessive collection and extended growth (4–5 years). This research shows that H+-ATPase activity was a key factor for oxalate-inducing programmed cell death (PCD) of P. tunicoides suspension cells. Oxalic acid (OA) is an effective abiotic elicitor that enhances a plant cell’s resistance to environmental stress. However, the role of OA in this process remains to be mechanistically unveiled. The present study evaluated the role of OA-induced cell death using an inverted fluorescence microscope after staining with Evans blue, FDA, PI, and Rd123. OA-stimulated changes in K+ and Ca2+ trans-membrane flows using a patch-clamp method, together with OA modulation of H+-ATPase activity, were further examined. OA treatment increased cell death rate in a dosage-and duration-dependent manner. OA significantly decreased the mitochondria activity and damaged its electron transport chain. The OA treatment also decreased intracellular pH, while the FC increased the pH value. Simultaneously, NH4Cl caused intracellular acidification. The OA treatment independently resulted in 90% and the FC led to 25% cell death rates. Consistently, the combined treatments caused a 31% cell death rate. Furthermore, treatment with EGTA caused a similar change in intracellular pH value to the La3+ and OA application. Combined results suggest that OA-caused cell death could be attributed to intracellular acidification and the involvement of OA in the influx of extracellular Ca2+, thereby leading to membrane depolarization. Here we explore the resistance mechanism of P. tunicoides cells against various stresses endowed by OA treatment.

scholarly journals Pro-apoptotic caspase deficiency reveals a cell-extrinsic mechanism of NK cell regulation

2021 ◽  
Author(s):  
Tayla M. Olsen ◽  
Wei Hong Tan ◽  
Arne C. Knudsen ◽  
Anthony Rongvaux
Keyword(s):  
Cell Death ◽  
Nk Cells ◽  
Nk Cell ◽  
Apoptotic Cell ◽  
Type I ◽  
Dependent Manner ◽  
Apoptosis Pathway ◽  
A Cell

AbstractRegulated cell death is essential for the maintenance of cellular and tissue homeostasis. In the hematopoietic system, genetic defects in apoptotic cell death generally produce the accumulation of immune cells, inflammation and autoimmunity. In contrast, we found that genetic deletion of caspases of the mitochondrial apoptosis pathway reduces natural killer (NK) cell numbers and makes NK cells functionally defective in vivo and in vitro. Caspase deficiency results in constitutive activation of a type I interferon (IFN) response, due to leakage of mitochondrial DNA and activation of the cGAS/STING pathway. The NK cell defect in caspase-deficient mice is independent of the type I IFN response, but the phenotype is partially rescued by cGAS or STING deficiency. Finally, caspase deficiency alters NK cells in a cell-extrinsic manner. Type I IFNs and NK cells are two essential effectors of antiviral immunity, and our results demonstrate that they are both regulated in a caspase-dependent manner. Beyond caspase-deficient animals, our observations may have implications in infections that trigger mitochondrial stress and caspase-dependent cell death.

Sign in / Sign up

Export Citation Format

Share Document