Mechanism of Puerariae Lobatae Radix against lung cancer by inhibiting histone demethylase LSD1.
10.19540/j.cnki.cjcmm.20220421.705
- Author:
Ting-Ting QIN
1
;
Jin-Lian MA
2
;
Yong YUAN
2
;
Kun DU
3
;
Jin-Xin MIAO
2
;
Xiao-Fang LI
2
;
Hua-Hui ZENG
2
;
Xiang-Xiang WU
2
;
Zhong-Hua LI
2
Author Information
1. Academy of Chinese Medical Sciences, Henan University of Chinese Medicine Zhengzhou 450046, China School of Pharmacy, Henan University of Chinese Medicine Zhengzhou 450046, China.
2. Academy of Chinese Medical Sciences, Henan University of Chinese Medicine Zhengzhou 450046, China.
3. School of Pharmacy, Henan University of Chinese Medicine Zhengzhou 450046, China.
- Publication Type:Journal Article
- Keywords:
LSD1;
Puerariae Lobatae Radix;
anti-tumor activity;
epithelial-mesenchymal transition;
lung cancer
- MeSH:
Pueraria/chemistry*;
Histone Demethylases/analysis*;
Plant Roots/chemistry*;
Epithelial-Mesenchymal Transition;
Neoplasms
- From:
China Journal of Chinese Materia Medica
2022;47(20):5574-5583
- CountryChina
- Language:Chinese
-
Abstract:
Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.