Ting-ting Qin - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China
Zhong-hua Li - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China
Li-xin Li - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China
Kun Du - School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan province, China
Ji-ge Yang - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China
Zhenqiang Zhang - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China
Xiang-xiang Wu - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China
Jinlian Ma - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou ۴۵۰۰۴۶, Henan Province, China

Objective(s): Lysine-specific demethylase۱ (LSD۱), an important class of histone demethylases, plays a crucial role in regulation of mammalian biology. The up-regulated LSD۱ expression was frequently associated with progress and oncogenesis of multiple human cancers, including non-small cell lung cancer (NSCLC). Therefore, inhibition of LSD۱ may provide an attractive strategy for cancer treatment. We investigated the effect of sanguinarine against lung cancer cells as a natural alkaloid LSD۱ inhibitor. Materials and Methods: The inhibition properties of sanguinarine to the recombinant LSD۱ were evaluated by a fluorescence-based method. Subsequently, assays such as viability, apoptosis, clonogenicity, wound healing, and transwell were performed on H۱۲۹۹ and H۱۹۷۵ cells after treatment with sanguinarine.Results: Upon screening our in-house natural chemical library toward LSD۱, we found that sanguinarine possessed a potent inhibitory effect against LSD۱ with the IC۵۰ value of ۰.۴ μM in a reversible manner. Molecular docking simulation suggested that sanguinarine may inactivate LSD۱ by inserting into the binding pocket of LSD۱ to compete with the FAD site. In H۱۲۹۹ and H۱۹۷۵ cells, sanguinarine inhibited the demethylation of LSD۱, validating its cellular activity against the enzyme. Further studies showed that sanguinarine exhibited a strong capacity to suppress colony formation, inhibit migration and invasion, as well as induce apoptosis of H۱۲۹۹ and H۱۹۷۵ cells. Conclusion: Our findings present a new chemical scaffold for LSD۱ inhibitors, and also provide new insight into the anti-NSCLC action of sanguinarine.

Antiproliferation, LSD۱ inhibitor, Migration, NSCLC, Sanguinarine