Drug Design, Development and Therapy (Jun 2024)
4-Deoxy-ϵ-Pyrromycinone: A Promising Drug/Lead Compound to Treat Tumors
Abstract
Jiping Zhang,* Xianan Sang,* Yichao Yuan, Jiawei Shen, Yuanyuan Fang, Minjing Qin, Hangsheng Zheng, Zhihong Zhu College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 311402, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hangsheng Zheng; Zhihong Zhu, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email [email protected]; [email protected]: Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy-ϵ-pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound.Methods: The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry.Results: In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype.Conclusion: In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo. Keywords: 4-deoxy-ϵ-pyrromycinone, lead compound, drug safety, drug efficacy, anti-tumor drug
