Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression - Aix-Marseille Université Access content directly
Journal Articles iScience Year : 2021

Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression

Abstract

Metabolic heterogeneity within the tumor microenvironment promotes cancer cell growth and immune suppression. We determined the impact of mitochondria-targeted complex I inhibitors (Mito-CI) in melanoma. Mito-CI decreased mitochondria complex I oxygen consumption, Akt-FOXO signaling, blocked cell cycle progression, melanoma cell proliferation and tumor progression in an immune competent model system. Immune depletion revealed roles for T cells in the antitumor effects of Mito-CI. While Mito-CI preferentially accumulated within and halted tumor cell proliferation, it also elevated infiltration of activated effector T cells and decreased myeloid-derived suppressor cells (MDSC) as well as tumor-associated macrophages (TAM) in melanoma tumors in vivo. Anti-proliferative doses of Mito-CI inhibited differentiation, viability, and the suppressive function of bone marrow-derived MDSC and increased proliferation-independent activation of T cells. These data indicate that targeted inhibition of complex I has synchronous effects that cumulatively inhibits melanoma growth and promotes immune remodeling.
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Dates and versions

hal-03627837 , version 1 (01-04-2022)

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Attribution - NonCommercial - NoDerivatives

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Mahmoud Abueid, Donna Mcallister, Laura Mcolash, Megan Harwig, Gang Cheng, et al.. Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression. iScience, 2021, 24 (6), pp.102653. ⟨10.1016/j.isci.2021.102653⟩. ⟨hal-03627837⟩
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