共查询到20条相似文献,搜索用时 15 毫秒
1.
Min You Medhi Wangpaichitr M. Tien Kuo Dao M. Nguyen 《Biochemical and biophysical research communications》2010,394(3):760-527
Current treatment for advanced, metastatic melanoma is not very effective, and new modalities are needed. ADI-PEG20 is a drug that specifically targets ASS-negative malignant melanomas while sparing the ASS-expressing normal cells. Although laboratory research and clinical trials showed promising results, there are some ASS-negative cell lines and patients that can develop resistance to this drug. In this report, we combined ADI-PEG20 with another antitumor drug TRAIL to increase the killing of malignant melanoma cells. This combination can greatly inhibit cell growth (to over 80%) and also enhanced cell death (to over 60%) in four melanoma cell lines tested compared with control. We found that ADI-PEG20 could increase the cell surface receptors DR4/5 for TRAIL and that caspase activity correlated with the increased cell death. These two drugs could also increase the level of Noxa while decrease that of survivin. We propose that these two drugs can complement each other by activating the intrinsic and extrinsic apoptosis pathways, thus enhance the killing of melanoma cells. 相似文献
2.
Jianying Qi Xianlong Ye Lingling Li Haijing Bai 《Bioscience, biotechnology, and biochemistry》2018,82(7):1153-1158
Onconase (ONC) as a novel anti-tumor drug has a significant killing effect on a variety of tumor cells. Drug delivery system mediated by transferrin (TF) and TF receptor (TfR), which can significantly increase the amount of drug uptake in the tumor cells, enhance the initiative target efficiency of drugs and reduce its toxic side effects. It has been widely used in drug delivery and clinical trials. In this study, the rONC-TFn was expressed in Escherichia coli by linking ONC with the N-terminal domain of TF (TFn). ELISA and competitive binding analysis demonstrated that rONC-TFn can bind to TfR. The rONC-TFn protein showed much higher cytotoxicity to the cultured HepG2 and Hela cells than rONC. These results suggested that the N-terminal domain protein of TF promoted the tumor targeting of ONC, and thus the rONC-TFn fusion protein may be further developed as a potential targeted anti-tumor drug. 相似文献
3.
Fernandez Gacio A Fernandez-Marcos C Swamy N Dunn D Ray R 《Journal of cellular biochemistry》2006,99(3):665-670
We hypothesized that estrogen receptor (ER) in hormone-sensitive breast cancer cells could be targeted for selective photodynamic killing of tumor cell with antiestrogen-porphyrin conjugates by combining the over-expression of ER in hormone-sensitive breast cancer cells and tumor-retention property of porphyrin photosensitizers. In this study we describe that a tamoxifen (TAM)-pyropheophorbide conjugate that specifically binds to ER alpha, caused selective cell-kill in MCF-7 breast cancer cells upon light exposure. Therefore, it is a potential candidate for ER-targeted photodynamic therapy of cancers (PDT) of tissues and organs that respond to estrogens/antiestrogens. 相似文献
4.
Summary It has been demonstrated that the carotenoid pigments of Sarcina lutea prevent photodynamic killing by either exogenous or endogenous photosensitizers.Evidence has been presented which suggests that the locus of the lethal photooxidation is in or on the cell membrane. 相似文献
5.
Feuerstein T Berkovitch-Luria G Nudelman A Rephaeli A Malik Z 《Photochemical & photobiological sciences》2011,10(12):1926-1933
Multi-drug resistance of breast cancer is a major obstacle in chemotherapy of cancer treatments. Recently it was suggested that photodynamic therapy (PDT) can overcome drug resistance of tumors. ALA-PDT is based on the administration of 5-aminolevulinic acid (ALA), the natural precursor for the PpIX biosynthesis, which is a potent natural photosensitizer. In the present study we used the AlaAcBu, a multifunctional ALA-prodrug for photodynamic inactivation of drug resistant MCF-7/DOX breast cancer cells. Supplementation of low doses (0.2mM) of AlaAcBu to the cells significantly increased accumulation of PpIX in both MCF-7/WT and MCF-7/DOX cells in comparison to ALA, or ALA + butyric acid (BA). In addition, our results show that MCF-7/DOX cells are capable of producing higher levels of porphyrins than MCF-7/WT cells due to low expression of the enzyme ferrochelatase, which inserts iron into the tetra-pyrrol ring to form the end product heme. Light irradiation of the AlaAcBu treated cells activated efficient photodynamic killing of MCF-7/DOX cells similar to the parent MCF-7/WT cells, depicted by low mitochondrial enzymatic activity, LDH leakage and decreased cell survival following PDT. These results indicate that the pro-drug AlaAcBu is an effective ALA derivative for PDT treatments of multidrug resistant tumors. 相似文献
6.
Marina V. Shirmanova Ekaterina O. Serebrovskaya Konstantin A. Lukyanov Ludmila B. Snopova Marina A. Sirotkina Natalia N. Prodanetz Marina L. Bugrova Ekaterina A. Minakova Ilya V. Turchin Vladislav A. Kamensky Sergey A. Lukyanov Elena V. Zagaynova 《Journal of biophotonics》2013,6(3):283-290
KillerRed is known to be a unique red fluorescent protein displaying strong phototoxic properties. Its effectiveness has been shown previously for killing bacterial and cancer cells in vitro. Here, we investigated the photototoxicity of the protein on tumor xenografts in mice. HeLa Kyoto cell line stably expressing KillerRed in mitochondria and in fusion with histone H2B was used. Irradiation of the tumors with 593 nm laser led to photobleaching of KillerRed indicating photosensitization reaction and caused significant destruction of the cells and activation of apoptosis. The portion of the dystrophically changed cells increased from 9.9% to 63.7%, and the cells with apoptosis hallmarks from 6.3% to 14%. The results of this study suggest KillerRed as a potential genetically encoded photosensitizer for photodynamic therapy of cancer. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
7.
The effect of cytochalasin A and B, colchicine and vinblastine on tumor cell killing by macrophages activated in vitro with lymphocyte mediators was examined. Both cytochalasins reversibly inhibited the killing of tumor cells by activated macrophages. Kinetic studies with cytochalasin B suggested that this drug exerts its effect on an early step of the cytotoxic process. Additional studies revealed that the drug inhibited the binding of tumor cells by activated macrophages.Colchicine inhibited both the binding and the killing of tumor cells by activated macrophages, whereas its structural analogue, lumicolchicine, had no effect on either macrophage function.Vinblastine also inhibited the binding and killing of tumor cells. However, this drug no longer inhibited tumor cell binding at low concentrations (<10?6M) that still inhibited tumor cell killing. Further, vinblastine inhibited tumor cell killing when added late to an ongoing cytolytic reaction.These results suggest that the cytochalasins, colchicine and vinblastine inhibit macrophage mediated cytotoxicity by preventing intimate contact between the effector macrophages and their targets. In addition, vinblastine also appears to inhibit a later step of the cytolytic process, possibly the secretion of a cytotoxic macrophage product. 相似文献
8.
The photodynamic properties of a second-generation photodynamic sensitizer, meta-tetra(hydroxyphenyl)chlorin (mTHPC) were studied by dye-sensitized photoinactivation (650 nm) of HT29 human adenocarcinoma cells in culture. The photocytotoxicity of mTHPC in vitro depended on the presence of molecular oxygen. A strong inhibition of the photocytotoxicity of mTHPC was observed upon addition of sodium azide, a known singlet oxygen quencher. Photocytotoxicity was not inhibited by scavengers of superoxide anion radical, hydrogen peroxide and hydroxyl radicals. We suggest that mTHPC photosensitizes cell killing predominantly by type II, singlet oxygen-mediated photodynamic reactions. Illumination of cells preloaded with mTHPC induced peroxidation of membrane lipids. Inhibition of photoperoxidation by alpha-tocopherol (0.1 mM) present during illumination did not result in any decrease in toxicity, suggesting that reactions of lipid peroxidation play only a minor role in the overall photocytotoxic effect of mTHPC. 相似文献
9.
10.
Reza Hosseinzadeh Khatereh Khorsandi Ghader Hosseinzadeh 《Journal of biomolecular structure & dynamics》2018,36(9):2216-2223
The interaction of methylene blue (MB) as a photosensitizer with graphene oxide nano-sheets (GO) was examined in aqueous solution using UV-vis spectrophotometric techniques. MB–GO composites were prepared by mixing the solutions of GO nano-sheets and methylene blue due to interacting of the cationic methylene blue photosensitizer via electrostatic and π–π stacking or hydrophobic cooperative interactions. The cell killing potential of nanocomposite was examined on the MDA-MB-231 breast cancer cells in the absence and presence of red LED irradiation. The results demonstrated that the MB-GO nanocomposite has good performance in photodynamic therapy (PDT) during red LED irradiation. The cytotoxicity of nanocomposite caused reducing cell viability up to 20%. These effects would be due to the nano size structure of composite that could lead to effective cellular penetration. Also the significant difference has seen in lower concentrations of MB and MB-GO nanocomposite. The results show more than 40% increases in cell killing potential in lower concentrations of nanocomposite by using 2.5 μg/mL of each compound. The ratio of GO/MB can affect the interaction and higher ratios of graphene oxide (GO/MB > 1) can induce dimerization of MB. In lower concentrations and ratios of (GO/MB < 1) the free MB concentration increases and the electron shuttling effect of GO in photo activity decreases – which could affect the photocatalytic yield in PDT. The cell viability measurements confirm these effects on cancer cell killing potential of nanocomposite. According to microscopic and PDT assay results, the nanocomposite distribution and diffusion in cells enhanced the photochemical reaction yield in photodynamic therapy of MDA-MB-231 breast cancer cell line. 相似文献
11.
12.
Tracy L. Collins Elizabeth A. Markus Daniel J. Hassett Jayne B. Robinson 《Current microbiology》2010,61(5):411-416
Current studies have indicated the utility of photodynamic therapy using porphyrins in the treatment of bacterial infections.
Photoactivation of porphyrins results in the production of singlet oxygen (1O2) that damages biomolecules associated with cells and biofilms, e.g., proteins, polysaccharides, and DNA. The effect of a
cationic porphryin on P. aeruginosa PAO1 biofilms was assessed by exposing static biofilms to 5,10,15,20-tetrakis(1-methyl-pyridino)-21H,23H-porphine, tetra-p-tosylate salt (TMP) followed by irradiation. Biofilms were visualized using confocal laser scanning microscopy (CLSM) and
cell viability determined using the LIVE/DEAD BacLight viability assay and standard plate counts. At a concentration of 100 μM
TMP, there was substantial killing of P. aeruginosa PAO1 wild-type and pqsA mutant biofilms with little disruption of the biofilm matrix or structure. Exposure to 225 μM TMP resulted in almost complete
killing as well as the detachment of wild-type PAO1 biofilms. In contrast, pqsA mutant biofilms that contain less extracellular DNA remained intact. Standard plate counts of cells recovered from attached
biofilms revealed a 4.1-log10 and a 3.9-log10 reduction in viable cells of wild-type PAO1 and pqsA mutant strains, respectively. Our results suggest that the action of photoactivated TMP on P. aeruginosa biofilms is two-fold: direct killing of individual cells within biofilms and detachment of the biofilm from the substratum.
There was no evidence of porphyrin toxicity in the absence of light; however, biofilms pretreated with TMP without photoactivation
were substantially more sensitive to tobramycin than untreated biofilms. 相似文献
13.
Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state
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Mohammad Fallahi‐Sichani Verena Becker Benjamin Izar Gregory J Baker Jia‐Ren Lin Sarah A Boswell Parin Shah Asaf Rotem Levi A Garraway Peter K Sorger 《Molecular systems biology》2017,13(1)
14.
Expression of the light-inducible lipA gene in Arthrobacter photogonimos by photodynamic compounds and visible light was inhibited by washing cells with 1 M KCl. Addition of cell surface extract
to KCl-washed cells restored the induction. Washing cells with 1 M MgCl2 removed a 14-kDa polypeptide and concomitantly caused expression of lipA gene without photodynamic treatment. The purified 14-kDa polypeptide inhibited photodynamic induction of lipA gene. These results indicated that regulation of lipA gene expression occurred at the cell surface and involved positive and negative factors, probably through a signal transduction
system.
Received: 29 July 1998 / Accepted: 31 August 1998 相似文献
15.
Construction of photodynamic‐effect immunofluorescence probes by a complex of quantum dots,immunoglobulin G and chlorin e6 and their application in HepG2 cell killing
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Zheng‐Yu Yan Li‐Li Wang Meng‐Ying Fei Xin‐Ying Liu Yi‐Long Su Qing‐Qing Du Sheng‐Mei Wu 《Luminescence》2016,31(6):1174-1181
In this study, tri‐functional immunofluorescent probes (Ce6–IgG–QDs) based on covalent combinations of quantum dots (QDs), immunoglobulin G (IgG) and chlorin e6 (Ce6) were developed and their photodynamic ability to induce the death of cancer cells was demonstrated. Strategically, one type of second‐generation photosensitizer, Ce6, was first coupled with anti‐IgG antibody using the EDC/NHS cross‐linking method to construct the photosensitive immunoconjugate Ce6–IgG. Then, a complex of Ce6–IgG–QDs immunofluorescent probes was obtained in succession by covalently coupling Ce6–IgG to water soluble CdTe QDs. The as‐manufactured Ce6–IgG–QDs maintained the bio‐activities of both the antigen–antibody‐based tumour targeting effects of IgG and the photodynamic‐related anticancer activities of Ce6. By way of polyclonal antibody interaction with rabbit anti‐human epidermal growth factor receptor (anti‐EGFR antibody, N‐terminus), Ce6–IgG–QDs were labelled indirectly onto the surface of human hepatocarcinoma (HepG2) cells in cell recognition and killing experiments. The results indicated that the Ce6–IgG–QDs probes have excellent tumour cell selectivity and higher photosensitivity in photodynamic therapy (PDT) compared with Ce6 alone, due to their antibody‐based specific recognition and location of HepG2 cells and the photodynamic effects of Ce6 killed cells based on efficient fluorescence resonance energy transfer between QDs and Ce6. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
16.
Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression 总被引:2,自引:0,他引:2
Chiu SM Xue LY Azizuddin K Oleinick NL 《Apoptosis : an international journal on programmed cell death》2005,10(6):1357-1368
Cell death following photodynamic therapy (PDT) with the photosensitizer Pc 4 involves the intrinsic pathway of apoptosis.
To evaluate the importance of Bax in apoptosis after PDT, we compared the PDT responses of Bax-proficient (Bax+/−) and Bax knock-out (BaxKO) HCT116 human colon cancer cells. PDT induced a slow apoptotic process in HCT Bax+/− cells following a long delay in the activation of Bax and release of cytochrome c from mitochondria. Although cytochrome c was not released from mitochondria following PDT in BaxKO cells, an alternative mechanism of caspase-dependent apoptosis
with extensive chromatin and DNA degradation was found in these cells. This alternative process was less efficient and slower
than the normal apoptotic process observed in Bax+/− cells. Early events upon PDT, such as the loss of mitochondrial membrane potential, photodamage to Bcl-2, and activation
of p38 MAP kinase, were observed in both HCT116 cell lines. In spite of differences in the efficiency and mode of apoptosis
induced by PDT in the Bax+/− and BaxKO cells, they were found to be equally sensitive to killing by PDT, as determined by loss of clonogenicity. Thus,
for Pc 4-PDT, the commitment to cell death occurs prior to and independent of Bax activation, but the process of cellular
disassembly differs in Bax-expressing vs. non-expressing cells. 相似文献
17.
Megan R. Dreier 《Experimental cell research》2009,315(7):1085-2987
Aurora kinases are essential for mitosis and are candidate targets of novel chemotherapeutic agents. The inhibitors ZM447439, MK-0457 (VX-680) as well as Hesperadin have been used to dissect the roles of Aurora kinases in the cell cycle and have been tested clinically for the treatment of cancer. Here we have carried out a detailed kinetic analysis of two isogenic cell lines differing in p53 function and have compared the effects of ZM447439 and VE-465 (related to MK-0457). We find that p53 is needed for efficient cell cycle arrest when Aurora kinases are inhibited by either ZM447439 or VE-465. However, the p53-induced cell cycle block is neither immediate nor absolute. ZM447439 induced the localized accumulation of γH2A.X indicating that p53 induction by this drug occurs in response to DNA damage. Our analysis of the long-term effects of ZM447439 indicates that cells can evade killing by the drug, but not via a classical drug-resistance mechanism. Several mechanisms to explain how cells may evade killing by Aurora kinase inhibitors are described. 相似文献
18.
Dahle J Bagdonas S Kaalhus O Olsen G Steen HB Moan J 《Biochimica et biophysica acta》2000,1475(3):273-280
Treatment of MDCK II cells with the lipophilic photosensitizer tetra(3-hydroxyphenyl)porphyrin and light was found to induce a rapid apoptotic response in a large fraction of the cells. Furthermore, the distribution of apoptotic cells in microcolonies of eight cells was found to be different from the binomial distribution, indicating that the cells are not inactivated independently, but that a bystander effect is involved in cell killing by photodynamic treatment. The observation of a bystander effect disagrees with the common view that cells are inactivated only by direct damage and indicates that communication between cells in a colony plays a role in photosensitized induction of apoptosis. The degree of bystander effect was higher for cells dying by necrosis than for cell dying by apoptosis. 相似文献
19.
Duska Separovic Ameeta Kelekar Adi L. Tarca Jason S. Pierce 《Archives of biochemistry and biophysics》2010,494(1):101-377
The purpose of this study was to determine the sphingolipid (SL) profile in cells defective in autophagy protein ATG-7 and overall cell death after photodynamic therapy (PDT) with the photosensitizer Pc 4. MCF-7 human breast cancer cells with downregulated ATG-7 and their scrambled controls (Scr) were used. Exposure of ATG-7 knockdown cells to PDT led to increased cell killing. PDT evoked an early (2 h) greater global increase in ceramides in ATG-7 defective cells compared to Scr cells. The total increases in dihydroceramide (DHceramide) were significant at 2 and 24 h in both cell types post-PDT. The levels of sphingosine-1-phosphate (S1P) and sphingosine were decreased below resting levels at both time points irrespective of the cell type. The data imply that ceramide might be a marker of ATG-7 deficiency in cells sensitized to PDT. 相似文献
20.
A genetically encoded photosensitizer 总被引:2,自引:0,他引:2
Bulina ME Chudakov DM Britanova OV Yanushevich YG Staroverov DB Chepurnykh TV Merzlyak EM Shkrob MA Lukyanov S Lukyanov KA 《Nature biotechnology》2006,24(1):95-99
Photosensitizers are chromophores that generate reactive oxygen species (ROS) upon light irradiation. They are used for inactivation of specific proteins by chromophore-assisted light inactivation (CALI) and for light-induced cell killing in photodynamic therapy. Here we report a genetically encoded photosensitizer, which we call KillerRed, developed from the hydrozoan chromoprotein anm2CP, a homolog of green fluorescent protein (GFP). KillerRed generates ROS upon irradiation with green light. Whereas known photosensitizers must be added to living systems exogenously, KillerRed is fully genetically encoded. We demonstrate the utility of KillerRed for light-induced killing of Escherichia coli and eukaryotic cells and for inactivating fusions to beta-galactosidase and phospholipase Cdelta1 pleckstrin homology domain. 相似文献