Huang Fei, Liu Yan, Huang Jinhua, He Dongqing, Wu Qiong, Zeng Yongchang, Zhao Bin, Mei Wenjie
School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Department of Pharmacy, Guangzhou Institute of Traditional Chinese Medicine, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, 518000, China.
Chem Biol Interact. 2025 May 1;412:111469. doi: 10.1016/j.cbi.2025.111469. Epub 2025 Mar 7.
G-quadruplex (G4) DNA, prevalent in tumor cells, offers a potential anticancer target. This study examined TA-1, a tanshinone IIA derivative, for its antitumor activity against liver cancer. We found that TA-1 binds and stabilizes multiple G4 DNA,triggering DNA damage, suppressing the angiogenesis in vitro and in vivo and leading to cancer cell death. Notably, we confirmed TA-1's inhibitory effect on liver cancer cells and explored its mechanism, which involves stabilizing G4 DNA to mediate replication-stress-dependent DNA damage. Furthermore, TA-1 promotes 53BP1 expression, activating toxic NHEJ repair and leading to apoptotic cell death via the ATM-Chk2-p53 pathway. In vivo studies further supported these findings. In summary, TA-1 is a potent VEGF G-quadruplex stabilizer that inhibits liver cancer progression.
G-四链体（G4）DNA在肿瘤细胞中普遍存在，是一种潜在的抗癌靶点。本研究检测了丹参酮IIA衍生物TA-1对肝癌的抗肿瘤活性。我们发现TA-1能结合并稳定多种G4 DNA，引发DNA损伤，在体外和体内抑制血管生成并导致癌细胞死亡。值得注意的是，我们证实了TA-1对肝癌细胞的抑制作用并探索了其机制，该机制涉及稳定G4 DNA以介导复制应激依赖性DNA损伤。此外，TA-1促进53BP1表达，激活有毒的非同源末端连接修复，并通过ATM-Chk2-p53途径导致凋亡性细胞死亡。体内研究进一步支持了这些发现。总之，TA-1是一种有效的血管内皮生长因子G-四链体稳定剂，可抑制肝癌进展。
