Inhibiting autophagy enhances sulforaphane-induced apoptosis
10.1016/j.apsb.2020.12.009
- Author:
Zhaoming LU
1
;
Yandan REN
1
;
Li YANG
1
;
Ang JIA
1
;
Yi HU
1
;
Yu ZHAO
1
;
Wuduo ZHAO
2
;
Bin YU
1
;
Wen ZHAO
1
;
Jianying ZHANG
3
;
Guiqin HOU
1
Author Information
1. State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
2. Center of Advanced Analysis & Gene Sequencing, Zhengzhou University, Zhengzhou 450001, China.
3. Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China.
- Publication Type:Journal Article
- Keywords:
Autophagy;
Chloroquine;
Esophageal squamous cell carcinoma;
NRF2;
Sulforaphane
- From:
Acta Pharmaceutica Sinica B
2021;11(5):1246-1260
- CountryChina
- Language:English
-
Abstract:
Sulforaphane (SFN), a natural anti-tumor compound from cruciferous vegetables, has been reported to induce protective autophagy to cancer cells, which might impair the anti-tumor efficiency of SFN. However, the accurate function and mechanism of SFN inducing autophagy in cancers are still obscure, especially in esophageal squamous cell carcinoma (ESCC), one of malignancies with high incidence in North China. Here, we mainly explored the potential function of autophagy upon SFN treatment in ESCC and molecular mechanism. We demonstrated that SFN could inhibit cell proliferation and induce apoptosis by activating caspase pathway. Moreover, we found activation of NRF2 pathway by SFN was responsible for the induction of autophagy and also a disadvantage element to the anti-tumor effects of SFN on ESCC, indicating that SFN might induce protective autophagy in ESCC. We, therefore, investigated effects of autophagy inhibition on sensitivity of ESCC cells to SFN and found that chloroquine (CQ) could neutralize the activation of SFN on NRF2 and enhance the activation of SFN on caspase pathway, thus improved the anti-tumor efficiency of SFN on ESCC