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Protocatechuic aldehyde sensitizes BRAF-mutant melanoma cells to temozolomide through inducing FANCD2 degradation

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机构： [1]Engineering Research Center of Sichuan‑Tibet Traditional Medicinal Plant, Chengdu University, Chengdu 610106, China [2]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, China [3]School of Basic Medical Sciences, Chengdu University, Chengdu 610106, China [4]School of Pharmacy, Chengdu University, Chengdu 610106, China [5]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China [6]Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, Chengdu 610106, China [7]Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China

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关键词： Protocatechuic aldehyde Temozolomide Synergy FANCD2 Melanoma

摘要：

Temozolomide (TMZ)-based chemotherapy is a primary regimen for melanoma patients who have failed targeted therapy or immunotherapy. However, the low response rate of TMZ-based chemotherapy challenges the patients' prognosis. BRAFV600E mutation is the most frequently mutated site in melanoma. This study investigates the synergistic effect of protocatechuic aldehyde (PA) and temozolomide (TMZ) in killing BRAFV600E mutant melanoma cells and BRAF inhibitor-resistant melanoma cells as well as the underlying molecular mechanisms. We report that PA synergistically promoted TMZ cytotoxicity to both BRAF inhibitor-sensitive and BRAF inhibitor-resistant melanoma cells. Combination of PA and TMZ increased DNA double-strand breaks and elevated apoptosis. Mechanism study reveals that PA promoted TMZ cytotoxicity through inducing FANCD2 degradation. Our results suggest that PA is a potential compound for melanoma combinational chemotherapy, regardless of O-6-methylguanine-DNA methyltransferase (MGMT) status.© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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大类 | 4 区医学

小类 | 4 区肿瘤学

第一作者：

第一作者机构： [1]Engineering Research Center of Sichuan‑Tibet Traditional Medicinal Plant, Chengdu University, Chengdu 610106, China [2]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, China [4]School of Pharmacy, Chengdu University, Chengdu 610106, China

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通讯作者：

通讯机构： [1]Engineering Research Center of Sichuan‑Tibet Traditional Medicinal Plant, Chengdu University, Chengdu 610106, China [2]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, China [3]School of Basic Medical Sciences, Chengdu University, Chengdu 610106, China

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Protocatechuic aldehyde sensitizes BRAF-mutant melanoma cells to temozolomide through inducing FANCD2 degradation

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