A novel copper complex induces paraptosis in colon cancer cells via the activation of ER stress signalling.
Valentina Gandin,Maura Pellei,Francesco Tisato,Marina Porchia,Carlo Santini,Cristina Marzano +5 more
TLDR
Light is shed on the signaling pathways involved in paraptosis thus offering a new tool to overcome apoptosis‐resistance in colon cancer cells, and providing a mechanistic characterization of CP‐induced cancer cell death.Abstract:
Platinum anticancer drugs have been used for three decades despite their serious side effects and the emerging of resistance phenomena. Recently, a phosphine copper(I) complex, [Cu(thp)(4)][PF(6)] (CP), gained special attention because of its strong antiproliferative effects. CP killed human colon cancer cells more efficiently than cisplatin and oxaliplatin and it overcame platinum drug resistance. CP preferentially reduced cancer cell viability whereas non-tumour cells were poorly affected. Colon cancer cells died via a programmed cell death whose transduction pathways were characterized by the absence of hallmarks of apoptosis. The inhibition of 26S proteasome activities induced by CP caused intracellular accumulation of polyubiquitinated proteins and the functional suppression of the ubiquitin-proteasome pathway thus triggering endoplasmic reticulum stress. These data, providing a mechanistic characterization of CP-induced cancer cell death, shed light on the signaling pathways involved in paraptosis thus offering a new tool to overcome apoptosis-resistance in colon cancer cells.read more
Citations
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Journal ArticleDOI
Advances in copper complexes as anticancer agents.
Carlo Santini,Maura Pellei,Valentina Gandin,Marina Porchia,Francesco Tisato,Cristina Marzano +5 more
Journal ArticleDOI
Endoplasmic Reticulum Stress signalling - from basic mechanisms to clinical applications
Aitor Almanza,Antonio Carlesso,Chetan Chintha,Stuart Creedican,Dimitrios Doultsinos,Brian Leuzzi,Andreia Luís,Nicole McCarthy,Luigi Montibeller,Sanket More,Alexandra Papaioannou,Franziska Püschel,Maria Livia Sassano,Josip Skoko,Patrizia Agostinis,Jackie de Belleroche,Leif A. Eriksson,Simone Fulda,Adrienne M. Gorman,Sandra Healy,Andrey V. Kozlov,Cristina Muñoz-Pinedo,Markus Rehm,Eric Chevet,Afshin Samali +24 more
TL;DR: This review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology.
OtherDOI
Claudins and other tight junction proteins.
Dorothee Günzel,Michael Fromm +1 more
TL;DR: Two TJ protein families can be distinguished, claudins, comprising 27 members in mammals, and TJ-associated MARVEL proteins (TAMP), comprising occludin, tricellulin, and MarvelD3, which are linked to a multitude of TJ- associated regulatory and scaffolding proteins.
Journal ArticleDOI
Cytoplasmic vacuolization in cell death and survival.
TL;DR: New data on the molecular mechanisms of the vacuole formation and structure are reviewed to make a deeper insight into the role of cytoplasmic vacuolization in cell death and survival.
Journal ArticleDOI
Copper-dependent cytotoxicity of 8-hydroxyquinoline derivatives correlates with their hydrophobicity and does not require caspase activation.
Saverio Tardito,Amelia Barilli,Irene Bassanetti,Matteo Tegoni,Ovidio Bussolati,Renata Franchi-Gazzola,Claudio Mucchino,Luciano Marchiò +7 more
TL;DR: The results show that the paraptotic cell death induced by Cu(CQ) does not require nor involve caspases, giving an indication for the current clinical assessment of clioquinol as an antineoplastic agent.
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