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Nigel D. Priestley - One of the best experts on this subject based on the ideXlab platform.
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Nonactin Biosynthesis: Unexpected Patterns of Label Incorporation from 4,6-Dioxoheptanoate Show Evidence of a Degradation Pathway for Levulinate through Propionate in Streptomyces griseus
Journal of Natural Products, 2010Co-Authors: Jian Rong, Brian R. Kusche, Micheal E. Nelson, Nigel D. PriestleyAbstract:The polyketide Nonactin, a polyketide possessing antitumor and antibacterial activity, is produced by an unusual biosynthesis pathway in Streptomyces griseus that uses both enantiomers of the Nonactin precursor, nonactic acid. Despite many studies with labeled precursors, much of the biosynthesis pathway remains unconfirmed, particularly the identity of the last achiral intermediate in the pathway, which is believed to be 4,6-diketoheptanoyl-CoA. We set out to confirm the latter hypothesis with feeding studies employing [4,5-13C2]-, [5,6-13C2]-, and [6,7-13C2]-4,6-diketoheptanoate thioester derivatives. In each case the isotopic label was incorporated efficiently into Nonactin; however, at positions inconsistent with the currently accepted biosynthesis pathway. To resolve the discrepancy, we conducted additional feeding studies with a [3,4-13C2]levulinate thioester derivative and again observed efficient label incorporation. The latter result was intriguing, as levulinate is not an obvious precursor to no...
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Alternating Pattern of Stereochemistry in the Nonactin Macrocycle Is Required for Antibacterial Activity and Efficient Ion Binding
Journal of the American Chemical Society, 2009Co-Authors: Brian R. Kusche, Adrienne E. Smith, Michele A. Mcguirl, Nigel D. PriestleyAbstract:Nonactin is a polyketide antibiotic produced by Streptomyces griseus ETH A7796 and is an ionophore that is selective for K+ ions. It is a cyclic tetraester generated from two monomers of (+)-nonactic acid and two of (−)-nonactic acid, arranged (+)-(−)-(+)-(−) so that Nonactin has S4 symmetry and is achiral. To understand why achiral Nonactin is the naturally generated diastereoisomer, we generated two alternate diastereoisomers of Nonactin, one prepared solely from (+)-nonactic acid and one prepared solely from (−)-nonactic acid, referred to here as ‘all-(+)-Nonactin’ and ‘all-(−)-Nonactin’, respectively. Both non-natural diastereoisomers were 500-fold less active against Gram positive organisms than Nonactin confirming that the natural stereochemistry is necessary for biological activity. We used isothermal calorimetry to obtain the Ka, ΔG, ΔH, and ΔS of formation for the K+, Na+, and NH4+ complexes of Nonactin and all-(−)-Nonactin; the natural diastereoisomer bound K+ 880-fold better than all-(−)-nonact...
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Nonactin biosynthesis: setting limits on what can be achieved with precursor-directed biosynthesis.
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Brian R. Kusche, Joshua B. Phillips, Nigel D. PriestleyAbstract:Abstract Nonactin, produced by Streptomyces griseus ETH A7796, is a macrotetrolide assembled from nonactic acid. It is an effective inhibitor of drug efflux in multidrug resistant erythroleukemia K562 cells at sub-toxic concentrations and has been shown to possess both antibacterial and antitumor activity. As total synthesis is impractical for the generation of Nonactin analogs we have studied precursor-directed biosynthesis as an alternative as it is known that nonactic acid can serve as a Nonactin precursor in vivo. To determine the scope of the approach we prepared and evaluated a furan-based nonactic acid derivative, 11 . Although no new Nonactin analogs were detected when 11 was administered to S. griseus fermentative cultures, a significant inhibition of Nonactin biosynthesis was noted (IC 50 ∼ 100 μM). Cell mass, nonactic acid production and the generation of other secondary metabolites in the culture were unaffected by 11 demonstrating that 11 selectively inhibited the assembly of Nonactin from nonactic acid. While we were unable to generate new Nonactin analogs we have discovered, however, a useful inhibitor that we can use to probe the mechanism of Nonactin assembly with the ultimate goal of developing more successful precursor-directed biosynthesis transformations.
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Nonactin biosynthesis: the product of the resistance gene degrades Nonactin stereospecifically to form homochiral nonactate dimers.
Journal of the American Chemical Society, 2005Co-Authors: James E. Cox, Nigel D. PriestleyAbstract:Heterologous expression of the tetranactin resistance gene nonR in E. coli gave a his6-tagged protein that catalyzed the stereoselective hydrolysis of the chiral macrotetrolide antibiotic Nonactin into equivalent, chiral, inactive nonactate dimer species. No trimeric nonactate was produced in the reaction.
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Nonactin biosynthesis: the initial committed step is the condensation of acetate (malonate) and succinate.
Journal of the American Chemical Society, 2002Co-Authors: Michael E. Nelson, Nigel D. PriestleyAbstract:Nonactin is a macrotetrolide antibiotic produced by Streptomyces griseus subsp. griseus ETH A7796 that has shown activity against the P170-glycoprotein efflux pump associated with multiple drug resistant cancer cells. Nonactin is a polyketide, albeit a highly atypical one. The structure is composed of two units of each of the enantiomers of nonactic acid, arranged in a macrocycle, so that the molecule has S4 symmetry and is achiral. The monomer units, (+)- and (−)-nonactic acid, are derived from acetate, succinate, and propionate, although the exact details of the assembly process are quite unclear. We have used feeding experiments with a series of multiple stable isotope labeled precursors to elucidate the details of the first committed step of nonactic acid biosynthesis. We have found that the 13C label from 3-ketoadipate is incorporated specifically into both nonactic acid and its homologue, homononactic acid. The data conclusively show that the first committed step of Nonactin biosynthesis is the coup...
Olga V. Yagodina - One of the best experts on this subject based on the ideXlab platform.
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increase in the toxic effects of tl on isolated rat liver mitochondria in the presence of Nonactin
Journal of Biochemical and Molecular Toxicology, 2007Co-Authors: Sergey M. Korotkov, Vadim V. Glazunov, Olga V. YagodinaAbstract:The effects of Tl+ ions on isolated rat liver mitochondria were studied in the presence of Nonactin, a cyclic ionophore. Nonenergized rat liver mitochondria were increasingly swollen at an elevated concentration of Tl+ in the 160 mOsm medium containing 0–150 mM sucrose and 0–75 mM TlNO3 or 0–50 mM Tl acetate. On the contrary, mitochondria in experiments with Nonactin were contracted in the medium with 5–25 mM Tl+ and were swollen only in the medium with 50–75 mM TlNO3 or 50 mM Tl acetate. State 4 respiration along with swelling of succinate-energized mitochondria followed contraction after their deenergization was further enhanced at increasing concentration of Tl acetate in a medium containing Nonactin. Regardless of the presence of Nonactin, State 3 and 2,4-dinitrophenol (DNP)-stimulated respiration and the monoamine oxidase (MAO) activity were not affected in the medium with 0–25 mM Tl acetate and sucrose. DNP-stimulated respiration decreased and the MAO activity somewhat increased in the medium containing 50 mM Tl acetate and Nonactin. Uptake of 86Rb+ by energized mitochondria in the presence of valinomycin was considerably decreased when Tl+ and Nonactin were simultaneously present in the medium. An increase of the toxic effect of Tl+ on rat liver mitochondria in the presence of Nonactin is accounted for by disruption of mitochondria due to their more extensive swelling and uncoupling of mitochondria, resulting in the stimulation of State 4 and depletion of their energy store. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:81–91, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20163
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Increase in the toxic effects of Tl+ on isolated rat liver mitochondria in the presence of Nonactin.
Journal of Biochemical and Molecular Toxicology, 2007Co-Authors: Sergey M. Korotkov, Vadim V. Glazunov, Olga V. YagodinaAbstract:The effects of Tl+ ions on isolated rat liver mitochondria were studied in the presence of Nonactin, a cyclic ionophore. Nonenergized rat liver mitochondria were increasingly swollen at an elevated concentration of Tl+ in the 160 mOsm medium containing 0–150 mM sucrose and 0–75 mM TlNO3 or 0–50 mM Tl acetate. On the contrary, mitochondria in experiments with Nonactin were contracted in the medium with 5–25 mM Tl+ and were swollen only in the medium with 50–75 mM TlNO3 or 50 mM Tl acetate. State 4 respiration along with swelling of succinate-energized mitochondria followed contraction after their deenergization was further enhanced at increasing concentration of Tl acetate in a medium containing Nonactin. Regardless of the presence of Nonactin, State 3 and 2,4-dinitrophenol (DNP)-stimulated respiration and the monoamine oxidase (MAO) activity were not affected in the medium with 0–25 mM Tl acetate and sucrose. DNP-stimulated respiration decreased and the MAO activity somewhat increased in the medium containing 50 mM Tl acetate and Nonactin. Uptake of 86Rb+ by energized mitochondria in the presence of valinomycin was considerably decreased when Tl+ and Nonactin were simultaneously present in the medium. An increase of the toxic effect of Tl+ on rat liver mitochondria in the presence of Nonactin is accounted for by disruption of mitochondria due to their more extensive swelling and uncoupling of mitochondria, resulting in the stimulation of State 4 and depletion of their energy store. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:81–91, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20163
Masaya Imoto - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial uncoupler exerts a synthetic lethal effect against β‐catenin mutant tumor cells
Cancer Science, 2017Co-Authors: Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya ImotoAbstract:The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated Nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of Nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as Nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. This article is protected by copyright. All rights reserved.
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mitochondrial uncoupler exerts a synthetic lethal effect against β catenin mutant tumor cells
Cancer Science, 2017Co-Authors: Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya ImotoAbstract:The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated Nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of Nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as Nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. This article is protected by copyright. All rights reserved.
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Abstract B68: Screening for the compound that induces cell death selectively in β-catenin mutant tumor cells
Drug Screening, 2015Co-Authors: Yuki Shikata, Masaki Kiga, Etsu Tashiro, Masaya ImotoAbstract:The Wnt signal transduction pathway plays a central role for the cell proliferation, differentiation and apoptosis. β-catenin, a component of Wnt pathway, translocates to nucleus and forms an active complex with TCF4, leading to activate cell growth signaling, and this activity is tightly regulated by the “destruction complex” consisting of Axin, APC, GSK3β and CK1α. However, when β-catenin is actively mutated, this cell growth signaling would be hyperactive and drive oncogenesis. As β-catenin is mutated in up to 10% of all sporadic colon carcinomas resulting from point mutations or in-frame deletions of serine and threonine residues phosphorylated by GSK3β, mutated β-catenin has been considered as promising targets for therapeutic intervention. Therefore, we screened the compound that induced cell death selectively in tumor cell lines harboring β-catenin mutation from an in-house natural product library, and finally we isolated and found that Nonactin, a well-known antibiotics, exhibited this activity. To confirm its apoptosis-inducing ability selectivity in β-catenin mutated cell lines, we examined the effect of Nonactin on cell viability in 15 human tumor cell lines. Nonactin potently induced PARP-cleavage in 5 cell lines harboring β-catenin mutation (A427, HCT116, LS-174T, SK-MEL-1, SW48 cells), whereas the others, which do not harbor a mutation of β-catenin activation, were resistant to Nonactin. In addition, overexpression of actively mutated β-catenin accelerated apoptosis induced by Nonactin in the Nonactin-resistant A375 cells, and β-catenin knockdown by siRNA reduced Nonactin-induced apoptosis in HCT116 cells. Furthermore, Nonactin induced tumor regression only in β-catenin mutated HCT116 xenograft mice. Taken together, these findings suggested that the β-catenin mutated tumor cell lines are highly sensitive to Nonactin, and it would be potential drug-seed for tumor cells harboring β-catenin mutation. Citation Format: Yuki Shikata, Masaki Kiga, Etsu Tashiro, Masaya Imoto. Screening for the compound that induces cell death selectively in β-catenin mutant tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B68.
Sergey M. Korotkov - One of the best experts on this subject based on the ideXlab platform.
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increase in the toxic effects of tl on isolated rat liver mitochondria in the presence of Nonactin
Journal of Biochemical and Molecular Toxicology, 2007Co-Authors: Sergey M. Korotkov, Vadim V. Glazunov, Olga V. YagodinaAbstract:The effects of Tl+ ions on isolated rat liver mitochondria were studied in the presence of Nonactin, a cyclic ionophore. Nonenergized rat liver mitochondria were increasingly swollen at an elevated concentration of Tl+ in the 160 mOsm medium containing 0–150 mM sucrose and 0–75 mM TlNO3 or 0–50 mM Tl acetate. On the contrary, mitochondria in experiments with Nonactin were contracted in the medium with 5–25 mM Tl+ and were swollen only in the medium with 50–75 mM TlNO3 or 50 mM Tl acetate. State 4 respiration along with swelling of succinate-energized mitochondria followed contraction after their deenergization was further enhanced at increasing concentration of Tl acetate in a medium containing Nonactin. Regardless of the presence of Nonactin, State 3 and 2,4-dinitrophenol (DNP)-stimulated respiration and the monoamine oxidase (MAO) activity were not affected in the medium with 0–25 mM Tl acetate and sucrose. DNP-stimulated respiration decreased and the MAO activity somewhat increased in the medium containing 50 mM Tl acetate and Nonactin. Uptake of 86Rb+ by energized mitochondria in the presence of valinomycin was considerably decreased when Tl+ and Nonactin were simultaneously present in the medium. An increase of the toxic effect of Tl+ on rat liver mitochondria in the presence of Nonactin is accounted for by disruption of mitochondria due to their more extensive swelling and uncoupling of mitochondria, resulting in the stimulation of State 4 and depletion of their energy store. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:81–91, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20163
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Increase in the toxic effects of Tl+ on isolated rat liver mitochondria in the presence of Nonactin.
Journal of Biochemical and Molecular Toxicology, 2007Co-Authors: Sergey M. Korotkov, Vadim V. Glazunov, Olga V. YagodinaAbstract:The effects of Tl+ ions on isolated rat liver mitochondria were studied in the presence of Nonactin, a cyclic ionophore. Nonenergized rat liver mitochondria were increasingly swollen at an elevated concentration of Tl+ in the 160 mOsm medium containing 0–150 mM sucrose and 0–75 mM TlNO3 or 0–50 mM Tl acetate. On the contrary, mitochondria in experiments with Nonactin were contracted in the medium with 5–25 mM Tl+ and were swollen only in the medium with 50–75 mM TlNO3 or 50 mM Tl acetate. State 4 respiration along with swelling of succinate-energized mitochondria followed contraction after their deenergization was further enhanced at increasing concentration of Tl acetate in a medium containing Nonactin. Regardless of the presence of Nonactin, State 3 and 2,4-dinitrophenol (DNP)-stimulated respiration and the monoamine oxidase (MAO) activity were not affected in the medium with 0–25 mM Tl acetate and sucrose. DNP-stimulated respiration decreased and the MAO activity somewhat increased in the medium containing 50 mM Tl acetate and Nonactin. Uptake of 86Rb+ by energized mitochondria in the presence of valinomycin was considerably decreased when Tl+ and Nonactin were simultaneously present in the medium. An increase of the toxic effect of Tl+ on rat liver mitochondria in the presence of Nonactin is accounted for by disruption of mitochondria due to their more extensive swelling and uncoupling of mitochondria, resulting in the stimulation of State 4 and depletion of their energy store. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:81–91, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20163
Yuki Shikata - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial uncoupler exerts a synthetic lethal effect against β‐catenin mutant tumor cells
Cancer Science, 2017Co-Authors: Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya ImotoAbstract:The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated Nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of Nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as Nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. This article is protected by copyright. All rights reserved.
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mitochondrial uncoupler exerts a synthetic lethal effect against β catenin mutant tumor cells
Cancer Science, 2017Co-Authors: Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya ImotoAbstract:The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated Nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of Nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as Nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. This article is protected by copyright. All rights reserved.
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Abstract B68: Screening for the compound that induces cell death selectively in β-catenin mutant tumor cells
Drug Screening, 2015Co-Authors: Yuki Shikata, Masaki Kiga, Etsu Tashiro, Masaya ImotoAbstract:The Wnt signal transduction pathway plays a central role for the cell proliferation, differentiation and apoptosis. β-catenin, a component of Wnt pathway, translocates to nucleus and forms an active complex with TCF4, leading to activate cell growth signaling, and this activity is tightly regulated by the “destruction complex” consisting of Axin, APC, GSK3β and CK1α. However, when β-catenin is actively mutated, this cell growth signaling would be hyperactive and drive oncogenesis. As β-catenin is mutated in up to 10% of all sporadic colon carcinomas resulting from point mutations or in-frame deletions of serine and threonine residues phosphorylated by GSK3β, mutated β-catenin has been considered as promising targets for therapeutic intervention. Therefore, we screened the compound that induced cell death selectively in tumor cell lines harboring β-catenin mutation from an in-house natural product library, and finally we isolated and found that Nonactin, a well-known antibiotics, exhibited this activity. To confirm its apoptosis-inducing ability selectivity in β-catenin mutated cell lines, we examined the effect of Nonactin on cell viability in 15 human tumor cell lines. Nonactin potently induced PARP-cleavage in 5 cell lines harboring β-catenin mutation (A427, HCT116, LS-174T, SK-MEL-1, SW48 cells), whereas the others, which do not harbor a mutation of β-catenin activation, were resistant to Nonactin. In addition, overexpression of actively mutated β-catenin accelerated apoptosis induced by Nonactin in the Nonactin-resistant A375 cells, and β-catenin knockdown by siRNA reduced Nonactin-induced apoptosis in HCT116 cells. Furthermore, Nonactin induced tumor regression only in β-catenin mutated HCT116 xenograft mice. Taken together, these findings suggested that the β-catenin mutated tumor cell lines are highly sensitive to Nonactin, and it would be potential drug-seed for tumor cells harboring β-catenin mutation. Citation Format: Yuki Shikata, Masaki Kiga, Etsu Tashiro, Masaya Imoto. Screening for the compound that induces cell death selectively in β-catenin mutant tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B68.