Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway

Olga Vondálová Blanáthoma, Iva Jelínková, Árpád Szöor, Belma Skender, Karel Souček, Viktor Horváth, Alena Vaculová, Ladislav Anděra, Petr Sova, J. Szöllősi, Jiřina Hofmanová, G. Vereb, Alois Kozubík

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalCarcinogenesis
Volume32
Issue number1
DOIs
Publication statusPublished - 2011

Fingerprint

Platinum
Cisplatin
Apoptosis
Colonic Neoplasms
TNF-Related Apoptosis-Inducing Ligand Receptors
Neoplasms
Prostatic Neoplasms
Death Domain Receptors
Caspase 8
Caspases
Small Interfering RNA
Tumor Necrosis Factor-alpha
Cell Membrane
Ligands
Lipids
Cell Line
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research

Cite this

Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway. / Blanáthoma, Olga Vondálová; Jelínková, Iva; Szöor, Árpád; Skender, Belma; Souček, Karel; Horváth, Viktor; Vaculová, Alena; Anděra, Ladislav; Sova, Petr; Szöllősi, J.; Hofmanová, Jiřina; Vereb, G.; Kozubík, Alois.

In: Carcinogenesis, Vol. 32, No. 1, 2011, p. 42-51.

Research output: Contribution to journalArticle

Blanáthoma, OV, Jelínková, I, Szöor, Á, Skender, B, Souček, K, Horváth, V, Vaculová, A, Anděra, L, Sova, P, Szöllősi, J, Hofmanová, J, Vereb, G & Kozubík, A 2011, 'Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway', Carcinogenesis, vol. 32, no. 1, pp. 42-51. https://doi.org/10.1093/carcin/bgq220
Blanáthoma, Olga Vondálová ; Jelínková, Iva ; Szöor, Árpád ; Skender, Belma ; Souček, Karel ; Horváth, Viktor ; Vaculová, Alena ; Anděra, Ladislav ; Sova, Petr ; Szöllősi, J. ; Hofmanová, Jiřina ; Vereb, G. ; Kozubík, Alois. / Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway. In: Carcinogenesis. 2011 ; Vol. 32, No. 1. pp. 42-51.
@article{528b63fa596a4ed4925aed32d7af51a8,
title = "Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway",
abstract = "TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin.",
author = "Blan{\'a}thoma, {Olga Vond{\'a}lov{\'a}} and Iva Jel{\'i}nkov{\'a} and {\'A}rp{\'a}d Sz{\"o}or and Belma Skender and Karel Souček and Viktor Horv{\'a}th and Alena Vaculov{\'a} and Ladislav Anděra and Petr Sova and J. Sz{\"o}llősi and Jiřina Hofmanov{\'a} and G. Vereb and Alois Kozub{\'i}k",
year = "2011",
doi = "10.1093/carcin/bgq220",
language = "English",
volume = "32",
pages = "42--51",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway

AU - Blanáthoma, Olga Vondálová

AU - Jelínková, Iva

AU - Szöor, Árpád

AU - Skender, Belma

AU - Souček, Karel

AU - Horváth, Viktor

AU - Vaculová, Alena

AU - Anděra, Ladislav

AU - Sova, Petr

AU - Szöllősi, J.

AU - Hofmanová, Jiřina

AU - Vereb, G.

AU - Kozubík, Alois

PY - 2011

Y1 - 2011

N2 - TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin.

AB - TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin.

UR - http://www.scopus.com/inward/record.url?scp=79952117634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952117634&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgq220

DO - 10.1093/carcin/bgq220

M3 - Article

C2 - 21037225

AN - SCOPUS:79952117634

VL - 32

SP - 42

EP - 51

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 1

ER -