Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy.

Autor: Vianello C; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.; Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131, Padova, Italy., Cocetta V; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy., Catanzaro D; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy., Dorn GW 2nd; Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, 63110, USA., De Milito A; Sprint Bioscience, Huddinge, Sweden.; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden., Rizzolio F; Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, 30172, Venice, Italy.; Pathology Unit, Centro di Riferimento Oncologico di Aviano (C.R.O.) IRCCS, 33081, Aviano, Italy., Canzonieri V; Pathology Unit, Centro di Riferimento Oncologico di Aviano (C.R.O.) IRCCS, 33081, Aviano, Italy.; Department of Medical, Surgical and Health Sciences, University of Trieste, 34149, Trieste, Italy., Cecchin E; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081, Aviano, Italy., Roncato R; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081, Aviano, Italy., Toffoli G; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081, Aviano, Italy., Quagliariello V; Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy., Di Mauro A; Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy., Losito S; Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy., Maurea N; Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy., Scaffa C; Gynecologic Oncology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy., Sales G; Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131, Padova, Italy., Scorrano L; Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131, Padova, Italy.; Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy., Giacomello M; Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131, Padova, Italy. marta.giacomello@unipd.it.; Department of Biomedical Sciences, Via Ugo Bassi 58B, 35131, Padova, Italy. marta.giacomello@unipd.it., Montopoli M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy. monica.montopoli@unipd.it.; Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy. monica.montopoli@unipd.it.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2022 Apr 22; Vol. 13 (4), pp. 398. Date of Electronic Publication: 2022 Apr 22.
DOI: 10.1038/s41419-022-04741-9
Abstrakt: Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.
(© 2022. The Author(s).)
Databáze: MEDLINE
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