JYD01, a newly synthesized diterpenoid derivative, induces apoptosis in human gastric cancer cells through detaching hexokinase II from mitochondria
10.3969/j.issn.1001-1978.2021.06.023
- Author:
Nan SU
1
;
Xia-Xia FAN
2
;
Ai-Feng WANG
2
;
Yong-Cheng MA
2
Author Information
1. College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy
2. Dept of Pharmacy, Henan Provincial People's Hospital, Dept of Pharmacy of Centeral China Fuwai Hospital, Centeral China Fuwai Hospital of Zhengzhou University
- Publication Type:Journal Article
- Keywords:
antitumor;
apoptosis;
glycolysis;
hexokinase II;
mitochondria;
natural ent-kaurene diterpenoids
- From:
Chinese Pharmacological Bulletin
2021;37(6):871-877
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of JYD01, an ent-kaurane diterpenoid analog, on detaching hexokinase II (HK II) from mitochondria, and discuss the underlying mechanism of anti-gastric cancer cell proliferation. Methods MTT assay was performed to measure the effect of JYD01 on the growth capacity of human gastric cancer cell lines MGC-803 and BGC-823. The glycolysis of MGC-803 cells in response to JYD01 was analyzed using a Seahorse XFp extracellular flux analyzer by real-time measurements of the extracellular acidification rate (ECAR, indicative of glycolysis). The effect of JYD01 in mitochondrial membrane potential (MMP) and apoptosis was observed by a fluorescence microscopy. The apoptotic rate and the quantitative analysis of MMP falling of cell lines treated with JYD01 were analyzed by flow cytometry. The proteins were determined by Western blot. Results JYD01 observably inhibited the growth of MGC-803 and BGC-823 cells in a dose-dependent manner. JYD01 induced a dose-dependent detachment of HK II from mitochondria of MGC-803 cells, effectively reduced glycolysis, and caused the drop of MMP leading to the release of cytochrome c. 1, 2 and 4 μmol · L
