Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation

Genome instability, a hallmark of cancer, leads to endless mutations that eventually cause drug resistance against almost all chemotherapy drugs. This poses a significant obstacle to the success of cancer treatments. Here, we report that aurintricarboxylic acid (ATCA) effectively suppresses the mali...

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Main Authors: Keke Shang, Yang Chen, Jingjie Jin, Tong Wang, Gong Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1576685/full
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author Keke Shang
Yang Chen
Jingjie Jin
Tong Wang
Gong Zhang
author_facet Keke Shang
Yang Chen
Jingjie Jin
Tong Wang
Gong Zhang
author_sort Keke Shang
collection DOAJ
description Genome instability, a hallmark of cancer, leads to endless mutations that eventually cause drug resistance against almost all chemotherapy drugs. This poses a significant obstacle to the success of cancer treatments. Here, we report that aurintricarboxylic acid (ATCA) effectively suppresses the malignant phenotypes, including proliferation, migration, invasion, and clone formation, of cancer cells of multiple cancers, including cisplatin-resistant lung cancer cells, paclitaxel-resistant lung cancer cells, and doxorubicin-resistant breast cancer cells. Interestingly, ATCA does not cause acute cytotoxicity. Proteome analysis of the whole proteome and nascent chains showed that ATCA reduced translation initiation and thus reduced the abundance of the highly abundant respiratory chain complex. This lowered the potential of the mitochondrial membrane and thus restricted the energy production. This principle could be hardly circumvented by cancer cells and thus may serve as a promising and universal candidate for a second-line therapeutic agent to control cancer progression after drug resistance.
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institution Kabale University
issn 2234-943X
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-93c1cd6dfbb6491eb1f25bdac9f6d0112025-08-20T03:49:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15766851576685Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulationKeke ShangYang ChenJingjie JinTong WangGong ZhangGenome instability, a hallmark of cancer, leads to endless mutations that eventually cause drug resistance against almost all chemotherapy drugs. This poses a significant obstacle to the success of cancer treatments. Here, we report that aurintricarboxylic acid (ATCA) effectively suppresses the malignant phenotypes, including proliferation, migration, invasion, and clone formation, of cancer cells of multiple cancers, including cisplatin-resistant lung cancer cells, paclitaxel-resistant lung cancer cells, and doxorubicin-resistant breast cancer cells. Interestingly, ATCA does not cause acute cytotoxicity. Proteome analysis of the whole proteome and nascent chains showed that ATCA reduced translation initiation and thus reduced the abundance of the highly abundant respiratory chain complex. This lowered the potential of the mitochondrial membrane and thus restricted the energy production. This principle could be hardly circumvented by cancer cells and thus may serve as a promising and universal candidate for a second-line therapeutic agent to control cancer progression after drug resistance.https://www.frontiersin.org/articles/10.3389/fonc.2025.1576685/fullaurintricarboxylic acid (ATCA)drug resistancetranslation inhibitionsecond-line therapeutic agentmalignant behavior
spellingShingle Keke Shang
Yang Chen
Jingjie Jin
Tong Wang
Gong Zhang
Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation
Frontiers in Oncology
aurintricarboxylic acid (ATCA)
drug resistance
translation inhibition
second-line therapeutic agent
malignant behavior
title Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation
title_full Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation
title_fullStr Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation
title_full_unstemmed Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation
title_short Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation
title_sort aurintricarboxylic acid inhibits the malignant phenotypes of drug resistant cells via translation regulation
topic aurintricarboxylic acid (ATCA)
drug resistance
translation inhibition
second-line therapeutic agent
malignant behavior
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1576685/full
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AT yangchen aurintricarboxylicacidinhibitsthemalignantphenotypesofdrugresistantcellsviatranslationregulation
AT jingjiejin aurintricarboxylicacidinhibitsthemalignantphenotypesofdrugresistantcellsviatranslationregulation
AT tongwang aurintricarboxylicacidinhibitsthemalignantphenotypesofdrugresistantcellsviatranslationregulation
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