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Hauptverfasser: Zhou, Yu-Dong, Mahdi, Fakhri, Nagle, Nicholas M, Jekabsons, Mika B, Nagle, Dale G
Format: Artículo científico
Sprache:en
Veröffentlicht: Marine drugs 2025
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Online-Zugang:https://pubmed.ncbi.nlm.nih.gov/41440898/
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author Zhou, Yu-Dong
Mahdi, Fakhri
Nagle, Nicholas M
Jekabsons, Mika B
Nagle, Dale G
author_facet Zhou, Yu-Dong
Mahdi, Fakhri
Nagle, Nicholas M
Jekabsons, Mika B
Nagle, Dale G
Zhou, Yu-Dong
Mahdi, Fakhri
Nagle, Nicholas M
Jekabsons, Mika B
Nagle, Dale G
collection PubMed - marine biology
contents Mechanistic Investigation of Adociaquinone and Xestoquinone Derivatives in Breast Cancer Cells. Zhou, Yu-Dong Mahdi, Fakhri Nagle, Nicholas M Jekabsons, Mika B Nagle, Dale G Humans Animals Breast Neoplasms Cell Line, Tumor Cell Proliferation Porifera Antineoplastic Agents Female Quinones Signal Transduction Membrane Potential, Mitochondrial Oxygen Consumption Xestoquinone derivatives isolated from marine sponges exhibit a range of bioactivities, including the inhibition of HIF signaling, mitochondrial function, and tumor cell proliferation. Mechanistic investigation suggested that 14-hydroxymethylxestoquinone () acts as a protonophore. Although adociaquinones A () and B () each stimulated cellular oxygen consumption, neither affected mitochondrial membrane potential. Cell-based respiration studies revealed that adociaquinones restored sodium azide-stalled oxygen consumption and ascorbate enhanced this response, suggesting ascorbate-supported redox cycling as a possible mechanism by which adociaquinones suppress HIF and tumor cell proliferation. These xestoquinone derivatives activated cellular stress response pathways that inhibit protein translation by phosphorylating key regulatory proteins (i.e., eIF2α, eIF4E, and eEF2). Further, thiol-reducing agents NAC and DTT attenuated the monosubstituted xestoquinone derivatives' efficacy to inhibit HIF signaling, suggesting a potential mechanism of action that involves sulfhydryl modification.
format Artículo científico
id pubmed_41440898
institution PubMed
language en
publishDate 2025
publisher Marine drugs
record_format pubmed
spellingShingle Mechanistic Investigation of Adociaquinone and Xestoquinone Derivatives in Breast Cancer Cells.
Zhou, Yu-Dong
Mahdi, Fakhri
Nagle, Nicholas M
Jekabsons, Mika B
Nagle, Dale G
Humans
Animals
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Porifera
Antineoplastic Agents
Female
Quinones
Signal Transduction
Membrane Potential, Mitochondrial
Oxygen Consumption
Mechanistic Investigation of Adociaquinone and Xestoquinone Derivatives in Breast Cancer Cells. Zhou, Yu-Dong Mahdi, Fakhri Nagle, Nicholas M Jekabsons, Mika B Nagle, Dale G Humans Animals Breast Neoplasms Cell Line, Tumor Cell Proliferation Porifera Antineoplastic Agents Female Quinones Signal Transduction Membrane Potential, Mitochondrial Oxygen Consumption Xestoquinone derivatives isolated from marine sponges exhibit a range of bioactivities, including the inhibition of HIF signaling, mitochondrial function, and tumor cell proliferation. Mechanistic investigation suggested that 14-hydroxymethylxestoquinone () acts as a protonophore. Although adociaquinones A () and B () each stimulated cellular oxygen consumption, neither affected mitochondrial membrane potential. Cell-based respiration studies revealed that adociaquinones restored sodium azide-stalled oxygen consumption and ascorbate enhanced this response, suggesting ascorbate-supported redox cycling as a possible mechanism by which adociaquinones suppress HIF and tumor cell proliferation. These xestoquinone derivatives activated cellular stress response pathways that inhibit protein translation by phosphorylating key regulatory proteins (i.e., eIF2α, eIF4E, and eEF2). Further, thiol-reducing agents NAC and DTT attenuated the monosubstituted xestoquinone derivatives' efficacy to inhibit HIF signaling, suggesting a potential mechanism of action that involves sulfhydryl modification.
title Mechanistic Investigation of Adociaquinone and Xestoquinone Derivatives in Breast Cancer Cells.
topic Humans
Animals
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Porifera
Antineoplastic Agents
Female
Quinones
Signal Transduction
Membrane Potential, Mitochondrial
Oxygen Consumption
url https://pubmed.ncbi.nlm.nih.gov/41440898/