CGP74514A enhances TRAIL-induced apoptosis in breast cancer cells by reducing X-linked inhibitor of apoptosis protein.

CGP74514A enhances TRAIL-induced apoptosis in breast cancer cells by reducing X-linked inhibitor of apoptosis protein.

Anticancer research (2014-07-02)

Sojung Park, Sang-Mi Shim, Sang-Hee Nam, Ladislav Andera, Nayoung Suh, Inki Kim

ABSTRACT

Despite the selectivity of Tumor necrosis factor Related Apoptosis-Inducing Ligand (TRAIL) for cancer cell killing activity, breast cancer cells are resistant to TRAIL-induced apoptosis for various reasons. From a functionally-characterized small-molecule dataset, CGP74514A was identified as a TRAIL sensitizer in MCF-7 breast cancer cells. Combination of sub-toxic dose of TRAIL with CGP74514A was evaluated in three TRAIL-resistant breast cancer cells, MCF-7, T47D and SK-BR-3. In all tested cells, CGP74514A enhanced TRAIL sensitivity. Combination treatment triggered apoptotic events faster than single treatment. Regarding its mechanism of action, CGP74514A reduced cytosolic X-linked inhibitor of apoptosis protein (XIAP). Small interfering RNA-mediated knockdown experiments showed that reduction of XIAP is the reason of sensitization. CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.

MATERIALS

Product Number

Brand

Product Description

M8266

Sigma-Aldrich

Magnesium chloride, anhydrous, ≥98%

M4880

Sigma-Aldrich

Magnesium chloride, BioReagent, suitable for insect cell culture, ≥97.0%

208337

Sigma-Aldrich

Magnesium chloride, powder, <200 μm

449164

Sigma-Aldrich

Magnesium chloride, AnhydroBeads^™, −10 mesh, 99.9% trace metals basis

449172

Sigma-Aldrich

Magnesium chloride, AnhydroBeads^™, −10 mesh, 99.99% trace metals basis

19-0220

Sigma-Aldrich

Magnesium chloride, CP

EHU111091

Sigma-Aldrich

MISSION^® esiRNA, targeting human XIAP

S5886

Sigma-Aldrich

Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%

S8776

Sigma-Aldrich

Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture

S6150

Sigma-Aldrich

Sodium chloride, tablet

S3014

Sigma-Aldrich

Sodium chloride, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)

M8787

Sigma-Aldrich

Magnesium chloride solution, PCR Reagent, 25 mM MgCI₂solution for PCR

M1028

Sigma-Aldrich

Magnesium chloride solution, for molecular biology, 1.00 M±0.01 M

S6546

Sigma-Aldrich

Sodium chloride solution, 5 M

S5150

Sigma-Aldrich

Sodium chloride solution, 5 M in H₂O, BioReagent, for molecular biology, suitable for cell culture

A3509

Sigma-Aldrich

2-Aminopurine, ≥99%

S1679

Sigma-Aldrich

Sodium chloride, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%

S7653

Sigma-Aldrich

Sodium chloride, BioXtra, ≥99.5% (AT)

450006

Sigma-Aldrich

Sodium chloride, AnhydroBeads^™, −10 mesh, 99.999% trace metals basis

68475

Sigma-Aldrich

Magnesium chloride solution, BioUltra, for molecular biology, 2 M in H₂O

71386

Sigma-Aldrich

Sodium chloride solution, BioUltra, for molecular biology, ~5 M in H₂O

63036

Sigma-Aldrich

Magnesium chloride solution, BioUltra, for molecular biology, ~0.025 M in H₂O

71383

Sigma-Aldrich

Sodium chloride, tested according to Ph. Eur.

71387

Supelco

Sodium chloride, reference material for titrimetry, certified by BAM, >99.5%

71376

Sigma-Aldrich

Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)

T5694

Sigma-Aldrich

TRAIL human, recombinant, expressed in NSO cells, >97% (SDS-PAGE), lyophilized powder

63069

Sigma-Aldrich

Magnesium chloride solution, BioUltra, for molecular biology, ~1 M in H₂O

378860

Sigma-Aldrich

Sodium chloride, random crystals, optical grade, 99.9% trace metals basis

451940

Sigma-Aldrich

Sodium chloride-³⁵Cl, 99 atom % ³⁵Cl

T9701

Sigma-Aldrich

TRAIL human, recombinant, expressed in E. coli, ≥98% (SDS-PAGE and HPLC), lyophilized powder