A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/β-catenin signaling pathway

• DOI: 10.1016/j.ejmech.2018.06.046
• Publication Date: 2018-06-20T01:21:27Z
• Authors: Shuangwei Liu; Xian Gao; Lisong Zhang; Shuanglin Qin; Mingming Wei; Ning Liu; Rui Zhao; Benlong Li; Ye Meng; Gang Lin; Cheng Lu; Xinhua Liu; Maodun Xie; Tongtong Liu; Honggang Zhou; Min Qi; Guang Yang; Cheng Yang
• Keywords: 0301 basic medicine; Melanoma, Experimental; Antineoplastic Agents; Apoptosis; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Cell Line, Tumor; Drug Discovery; Neoplastic Stem Cells; Animals; Humans; Neoplasm Invasiveness; 14. Life underwater; Peptides; Melanoma; Wnt Signaling Pathway; Antimicrobial Cationic Peptides; Cell Proliferation

Cancer stem cells (CSCs) are responsible for carcinogenesis, cancer progression, relapse, metastasis and drug resistance. Therefore, the development of drug molecules targeting CSCs plays a vital role in medicinal researching field. However, there are extremely rare molecules that selectively ablate CSCs. The research and development of drugs targeting CSCs is limited due to a lack of anti-CSCs lead compounds. In this study, an anti-CSCs lead compound 35b was discovered, which was derived from the natural chemical scaffold of Symplostatin 4. This compound exhibited a significantly suppressive effect on tumor growth both in vitro and in vivo. Additionally, 35b could significantly reduce the number of melanoma tumor spheres and decrease the percentage of ALDH+ melanoma cells. Further mechanism study illustrated that compound 35b could eliminate the melanoma CSCs by efficiently blocking Wnt/β-catenin signaling pathway. Collectively, our findings would provide a novel chemical scaffold and alternative idea of molecular design for development of anti-CSCs drugs.