Shang Keke, Chen Yang, Jin Jingjie, Wang Tong, Zhang Gong
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and Ministry of Education Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Front Oncol. 2025 May 14;15:1576685. doi: 10.3389/fonc.2025.1576685. eCollection 2025.
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.
基因组不稳定是癌症的一个标志，会导致无休止的突变，最终产生对几乎所有化疗药物的耐药性。这对癌症治疗的成功构成了重大障碍。在此，我们报告金精三羧酸（ATCA）能有效抑制多种癌症的癌细胞的恶性表型，包括增殖、迁移、侵袭和克隆形成，这些癌症的癌细胞包括顺铂耐药肺癌细胞、紫杉醇耐药肺癌细胞和阿霉素耐药乳腺癌细胞。有趣的是，ATCA不会引起急性细胞毒性。对整个蛋白质组和新生链的蛋白质组分析表明，ATCA减少了翻译起始，从而降低了高度丰富的呼吸链复合物的丰度。这降低了线粒体膜电位，从而限制了能量产生。癌细胞很难规避这一原理，因此它可能成为一种有前景的通用二线治疗药物候选物，用于控制耐药后癌症的进展。
