Paris saponin VII, a direct activator of AMPK, induces autophagy and exhibits therapeutic potential in non-small-cell lung cancer.
10.1016/S1875-5364(21)60021-3
- Author:
Yu-Chen XIANG
1
,
2
;
Jie SHEN
1
,
2
;
Yuan SI
1
,
3
,
4
;
Xue-Wen LIU
4
,
5
;
Liang ZHANG
1
,
2
;
Jun WEN
1
,
2
;
Te ZHANG
5
,
6
;
Qing-Qing YU
5
,
6
;
Jun-Fei LU
1
,
2
;
Ke XIANG
7
;
Ying LIU
1
,
3
,
8
,
9
Author Information
1. Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China
2. Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry, Hubei University of Medicine, Shiyan 442000, China.
3. Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry, Hubei University of Medicine, Shiyan 442000, China
4. Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China.
5. Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry, Hubei University of Medicine, Shiyan 442000, China
6. Laboratory of Molecular Target Therapy of Cancer, Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China.
7. Department of Science and Education, Gucheng People's Hospital, Hubei University of Arts and Science, Xiangyang 441700, China.
8. Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China
9. Laboratory of Molecular Target Therapy of Cancer, Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China. Electronic address: ying_liu1002@163.com.
- Publication Type:Journal Article
- Keywords:
AMPK;
Autophagy;
NSCLC;
Paris saponin VII
- From:
Chinese Journal of Natural Medicines (English Ed.)
2021;19(3):195-204
- CountryChina
- Language:English
-
Abstract:
Paris saponin VII (PSVII), a bioactive constituent extracted from Trillium tschonoskii Maxim., is cytotoxic to several cancer types. This study was designed to explore whether PSVII prevents non-small-cell lung cancer (NSCLC) proliferation and to investigate its molecular target. AMP-activated protein kinase (AMPK) has been implicated in the activation of autophagy in distinct tissues. In cultured human NSCLC cell lines, PSVII induces autophagy by activating AMPK and inhibiting mTOR signaling. Furthermore, PSVII-induced autophagy activation was reversed by the AMPK inhibitor compound C. Computational docking analysis showed that PSVII directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSVII and AMPK. In summary, PSVII acts as a direct AMPK activator to induce cell autophagy, which inhibits the growth of NSCLC cells. In the future, PSVII therapy should be applied to treat patients with NSCLC.
