Selective Cytotoxic Activity of Valinomycin against HT-29 Human Colon Carcinoma Cells via Down-Regulation of GRP78

Ryoo, In‐Ja; Park, Hae-Ryong; Choo, Soo‐Jin; Hwang, Ji‐Hwan; Park, Young-Min; Bae, KiHwan; Shin‐ya, Kazuo; Yoo, Ick Dong

doi:10.1248/bpb.29.817

Cited by 40 publications

(26 citation statements)

References 25 publications

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“…Further support of the versipelostatin/biguanide signature usefulness is the finding that, according to Connectivity Map analysis, a potassium ionophore valinomycin and a protein kinase C inhibitor, rottlerin, were the high-ranked candidates for UPR-modulating compounds (see Supplementary Table S6). In fact, during the course of this study, valinomycin was shown to exert selective cytotoxicity to 2DG-treated cancer cells through down-regulation of GRP78 (43), and rottlerin was shown to suppress ER stressinduced autophagy, which is required for survival in response to ER stress (44).…”

Section: Discussionmentioning

confidence: 82%

Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation

et al. 2009

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Glucose deprivation, a cell condition that occurs in solid tumors, activates the unfolded protein response (UPR). A key feature of the UPR is the transcription program activation, which allows the cell to survive under stress conditions. Here, we show that the UPR transcription program is disrupted by the antidiabetic biguanides metformin, buformin, and phenformin depending on cellular glucose availability. These drugs inhibit production of the UPR transcription activators XBP1 and ATF4 and induce massive cell death during glucose deprivation as did the antitumor macrocyclic compound versipelostatin. Gene expression profiling shows remarkable similarity in the modes of action of biguanides and versipelostatin determined by the broad range of glucose deprivation-inducible genes. Importantly, during glucose deprivation, most of the biguanide suppression genes overlap with the genes induced by tunicamycin, a chemical UPR inducer. Gene expression profiling also identifies drug-driven signatures as a tool for discovering pharmacologic UPR modulators. Our findings show that disrupting the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical genomic basis for developing UPR-targeting drugs against solid tumors.

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Section: Discussionmentioning

confidence: 82%

Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation

et al. 2009

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“…Hydrophobic side chains of valine and hydroxyisovaleric acid allow for its diffusion through the hydrophobic interior of cell membranes, a process driven by the existing K ϩ and/or charge gradients (33). A wide range of biological activities has been reported for valinomycin, including insecticidal, nematicidal, antiviral, and apoptosis-inducing effects in human cells (11,62). Valinomycin has become a useful tool in the study of ion transport in biological systems, and its inhibitory effect on intact cells and the growth of bacteria and yeast has been studied, although to a limited extent (25,26,61,64).…”

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confidence: 99%

Comparative Analysis of Antimicrobial Activities of Valinomycin and Cereulide, the Bacillus cereus Emetic Toxin

Tempelaars

Rodrigues

Abee

2011

Appl Environ Microbiol

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Cereulide and valinomycin are highly similar cyclic dodecadepsipeptides with potassium ionophoric properties. Cereulide, produced by members of the Bacillus cereus group, is known mostly as emetic toxin, and no ecological function has been assigned. A comparative analysis of the antimicrobial activity of valinomycin produced by Streptomyces spp. and cereulide was performed at a pH range of pH 5.5 to pH 9.5, under anaerobic and aerobic conditions. Both compounds display pH-dependent activity against selected Gram-positive bacteria, including Staphylococcus aureus, Listeria innocua, Listeria monocytogenes, Bacillus subtilis, and Bacillus cereus ATCC 10987. Notably, B. cereus strain ATCC 14579 and the emetic B. cereus strains F4810/72 and A529 showed reduced sensitivity to both compounds, with the latter two strains displaying full resistance to cereulide. Both compounds showed no activity against the selected Gram-negative bacteria. Antimicrobial activity against Gram-positive bacteria was highest at alkaline pH values, where the membrane potential (⌬⌿) is the main component of the proton motive force (PMF). Furthermore, inhibition of growth was observed in both aerobic and anaerobic conditions. Determination of the ⌬⌿, using the membrane potential probe DiOC 2 (3) (in the presence of 50 mM KCl) in combination with flow cytometry, demonstrated for the first time the ability of cereulide to dissipate the ⌬⌿ in sensitive Gram-positive bacteria. The putative role of cereulide production in the ecology of emetic B. cereus is discussed.Members of the Bacillus cereus group, also known as Bacillus cereus sensu lato, are Gram-positive, rod-shaped, facultative anaerobic, spore-forming bacteria (30,31). This group consists of the species B. cereus, B. weihenstephanensis, B. mycoides, B. pseudomycoides, B. anthracis, and B. thuringiensis (16, 30, 31, 70). B. cereus is found predominantly in the soil (3,30,70,75) and has been isolated from the rhizosphere (3, 5), the air (70), the gut of invertebrates (30,39), and a wide range of foods (16,70). It is a notorious food spoilage organism (4, 70) and the causative agent of two types of food-borne disease (16,22,70), the emetic and diarrheal syndromes. The emetic toxin cereulide is produced by emetic B. cereus (1, 2, 22, 70) and some psychrotolerant B. weihenstephanensis strains (72,73). This food intoxication, expressed by vomiting, is usually mild but occasionally results in fatalities (12,42,70). The toxin was found to be proteolytic resistant and highly heat and pH stable (57,67,68,74). Cereulide is a so-called cyclic dodecadepsipep-, and its K ϩ ionophoric properties have been established in black-lipid membranes and by assessing its impact on mitochondrial swelling and function (1,32,45,68). Recent research focused mainly on the genetic factors involved in the production of cereulide, the identification of transcriptional regulators, detection methods, and the impact of environmental conditions on cereulide levels reached, including a variety of (model) foods (13,15,17,38,...

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“…Protein loading was controlled by probing the membranes for β-actin protein. Western blots were developed using the enhanced chemiluminescence detection kit (Amersham Pharmacia Biotech) according to the manufacture's instructions [19].…”

Section: Western Blot Analysismentioning

confidence: 99%

Methanolic Extracts of Uncaria rhynchophylla Induce Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells

Cha

Lee

et al. 2008

Plant Foods Hum Nutr

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In this paper, we report the anticancer activities of Uncaria rhynchophylla extracts, a Rubiaceae plant native to China. Traditionally, Uncaria rhynchophylla has been used in the prevention and treatment of neurotoxicity. However, the cytotoxic activity of Uncaria rhynchophylla against human colon carcinoma cells has not, until now, been elucidated. We found that the methanolic extract of Uncaria rhynchophylla (URE) have cytotoxic effects on HT-29 cells. The URE showed highly cytotoxic effects via the MTT reduction assay, LDH release assay, and colony formation assay. As expected, URE inhibited the growth of HT-29 cells in a dose-dependent manner. In particular, the methanolic URE of the 500 microg/ml showed 15.8% inhibition against growth of HT-29 cells. It induced characteristic apoptotic effects in HT-29 cells, including chromatin condensation and sharking occurring 24 h when the cells were treated at a concentration of the 500 microg/ml. The activation of caspase-3 and the specific proteolytic cleavage of poly (ADP-ribose) polymerase were detected over the course of apoptosis induction. These results indicate that URE contains bioactive materials with strong activity, and is a potential chemotherapeutic agent candidate against HT-29 human colon carcinoma cells.

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Selective Cytotoxic Activity of Valinomycin against HT-29 Human Colon Carcinoma Cells via Down-Regulation of GRP78

Cited by 40 publications

References 25 publications

Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation

Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation

Comparative Analysis of Antimicrobial Activities of Valinomycin and Cereulide, the Bacillus cereus Emetic Toxin

Methanolic Extracts of Uncaria rhynchophylla Induce Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells

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