Cordycepin inhibits pancreatic cancer cell growth in vitro and in vivo via targeting FGFR2 and blocking ERK signaling.
10.1016/S1875-5364(20)30041-8
- Author:
Xue-Ying LI
1
,
2
;
Homng TAO
3
;
Can JIN
3
;
Zhen-Yun DU
3
;
Wen-Feng LIAO
3
;
Qing-Jiu TANG
4
;
Kan DING
5
Author Information
1. Glycochemistry & Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, University of Chinese Academy of Sciences, Beijing 100049, China
2. College of Pharmacy, Nanchang University, Nanchang 330006, China.
3. Glycochemistry & Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, University of Chinese Academy of Sciences, Beijing 100049, China.
4. Institute of Edible Fungi, Shanghai Academy of Agricultural Science, Shanghai 201203, China. Electronic address: tangqingjiu@saas.sh.cn.
5. Glycochemistry & Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: dingkan@simm.ac.cn.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Cordycepin;
FGFR2;
Pancreatic cancer;
Ras/Erk
- From:
Chinese Journal of Natural Medicines (English Ed.)
2020;18(5):345-355
- CountryChina
- Language:English
-
Abstract:
Cordycepin (3'-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo. Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2 (checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2 (K = 7.77 × 10) very potently to inhibit pancreatic cancer cells growth by blocking Ras/ErK pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.
