Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, Fujian 350014, P.R. China.
Fujian Provincial Key Laboratory of Medical Instrument and Pharmaceutical Technology, College of Biological Science and Technology, Fuzhou University, Fuzhou, Fujian 350108, P.R. China.
Int J Mol Med. 2022 Oct;50(4). doi: 10.3892/ijmm.2022.5186. Epub 2022 Sep 2.
Being a highly conserved catabolic process, autophagy is induced by various forms of cellular stress, and its modulation has considerable potential as a cancer therapeutic approach. In the present study, it was demonstrated that dicitrinone B (DB), a rare carbon‑bridged citrinin dimer, may exert anticancer effects by blocking autophagy at a late stage, without disrupting lysosomal function in MCF7 breast cancer and MDA‑MB‑231 triple‑negative breast cancer cells. Furthermore, it was discovered that DB significantly enhanced intracellular reactive oxygen species (ROS) production and that the removal of ROS was followed by the attenuation of autophagy inhibition. In addition, DB exerted notable inhibitory effects on the proliferation and promoting effects on the apoptosis of MCF7 and MDA‑MB‑231 cells. In combination with conventional chemotherapeutic drugs, DB exhibited a further enhanced synergistic effect than when used as a single agent. Overall, the data of the present study demonstrate that DB may prove to be a promising autophagy inhibitor with anticancer activity against breast cancer.
自噬是一种高度保守的分解代谢过程，可被多种形式的细胞应激所诱导，其调控具有作为癌症治疗方法的巨大潜力。在本研究中，证明了二氢血根碱 B（DB），一种罕见的碳桥接桔霉素二聚体，可能通过在晚期阻断自噬而发挥抗癌作用，而不会破坏 MCF7 乳腺癌和 MDA-MB-231 三阴性乳腺癌细胞中的溶酶体功能。此外，发现 DB 可显著增加细胞内活性氧（ROS）的产生，并且在 ROS 去除后，自噬抑制作用减弱。此外，DB 对 MCF7 和 MDA-MB-231 细胞的增殖具有显著的抑制作用，并促进其凋亡。与常规化疗药物联合使用时，DB 表现出比单独使用时更强的协同增效作用。总体而言，本研究的数据表明，DB 可能是一种有前途的具有抗癌活性的自噬抑制剂，可用于治疗乳腺癌。
