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MCL-1 dependency of cisplatin-resistant cancer cells

Michels, Judith (författare)
Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
Obrist, Florine (författare)
Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Université Paris Sud, Villejuif, France
Vitale, Ilio (författare)
Regina Elena National Cancer Institute, Rome, Italy
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Lissa, Delphine (författare)
Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
Garcia, Pauline (författare)
Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
Behnam-Motlagh, Parviz (författare)
Umeå universitet,Klinisk kemi
Kohno, Kimitoshi (författare)
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
Wu, Gen Sheng (författare)
Department of Oncology and Pathology, School of Medicine, Wayne State University, MI, Detroit, United States
Brenner, Catherine (författare)
U769, INSERM-LabEx LERMIT, Faculté de Pharmacie, Châtenay Malabry, France
Castedo, Maria (författare)
Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
Kroemer, Guido (författare)
Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
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 (creator_code:org_t)
Elsevier, 2014
2014
Engelska.
Ingår i: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839. ; 92:1, s. 55-61
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The selection of human cancer cell lines in cis-diamminedichloroplatinum(II) (CDDP, best known as cisplatin) is accompanied by stereotyped alterations that contribute to the acquisition of a CDDP-resistant state. Thus, CDDP resistance often leads to the upregulation of the DNA repair enzyme poly (ADP-ribose) polymerase-1 (PARP1) with the consequent intracellular accumulation of poly (ADP-ribose) (PAR)-modified proteins. Here we report another frequent alteration accompanying CDDP resistance, namely upregulation of the antiapoptotic BCL-2 family protein MCL-1. Six out of 8 CDDP resistant cancer cell lines manifested an increase in MCL-1 protein expression level, while only a minority of cell lines overexpressed BCL-2 or BCL-XL. BCL-XL was decreased in six out of 8 cancer cell lines. Importantly, MCL-1 overexpressing, CDDP resistant cells appear to be 'addicted' to MCL-1 because they died upon depletion of MCL-1 by RNA interference or pharmacological inhibition of MCL-1 expression by the BH3 mimetic obatoclax. Knockdown of PARP1 did not succeed in reducing MCL-1 expression, while depletion or inhibition of MCL-1 failed to affect the activity of PARP1. Hence, the two resistance mechanisms are not linked to each other by a direct cause-effect relationship. Importantly, CDDP-resistant, MCL-1 overexpressing human non-small cell lung cancers responded to monotherapy with obatoclax in vivo, in xenotransplanted mice, underscoring the probable therapeutic relevance of these findings.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Apoptosis
Chemoresistance
MCL-1
Obatoclax
PARP1

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