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

VONDÁLOVÁ BLANÁŘOVÁ, Olga, Iva JELÍNKOVÁ, Arpad SZOEOR, Belma SKENDER, Karel SOUČEK, Viktor HORVÁTH, Alena VACULOVÁ, Ladislav ANDERA, Petr SOVA, Janos SZOELLOSI, Jiřina HOFMANOVÁ, Gyoergy VEREB and Alois KOZUBÍK. 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. Oxford: Oxford University Press, 2011, vol. 32, No 1, p. 42-51. ISSN 0143-3334. Available from: https://dx.doi.org/10.1093/carcin/bgq220.

Basic information

• Original name: 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
• Authors: VONDÁLOVÁ BLANÁŘOVÁ, Olga (203 Czech Republic, belonging to the institution), Iva JELÍNKOVÁ (203 Czech Republic, belonging to the institution), Arpad SZOEOR (348 Hungary), Belma SKENDER (70 Bosnia and Herzegovina), Karel SOUČEK (203 Czech Republic, belonging to the institution), Viktor HORVÁTH (203 Czech Republic, belonging to the institution), Alena VACULOVÁ (203 Czech Republic, belonging to the institution), Ladislav ANDERA (203 Czech Republic), Petr SOVA (203 Czech Republic), Janos SZOELLOSI (348 Hungary), Jiřina HOFMANOVÁ (203 Czech Republic), Gyoergy VEREB (348 Hungary) and Alois KOZUBÍK (203 Czech Republic, guarantor).
• Edition: Carcinogenesis, Oxford, Oxford University Press, 2011, 0143-3334.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30105 Physiology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 5.702
• RIV identification code: RIV/00216224:14310/11:00062480
• Organization unit: Faculty of Science
• Doi: http://dx.doi.org/10.1093/carcin/bgq220
• UT WoS: 000286303000007
• Keywords in English: MEMBRANE-LIPID RAFTS; CHEMOTHERAPEUTIC-AGENTS; IN-VITRO; CASPASE-8 ACTIVATION; CARCINOMA CELLS; INHIBITORY PROTEIN; ANTITUMOR-ACTIVITY; DEATH RECEPTORS; LIGAND TRAIL; II CELLS
• Tags: AKR, rivok

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.