Casticin inhibits proliferation of non-small cell lung cancer cells by regulating glucose metabolism through suppression of HIF-1α.
10.19540/j.cnki.cjcmm.20240802.703
- Author:
Jing-Yi WEI
1
;
Hui NING
1
;
Jia-Qi DONG
1
;
Le HAN
2
;
Wen-Juan CHEN
3
;
Guang-Yan LEI
2
Author Information
1. Shaanxi University of Chinese Medicine Xianyang 710046, China.
2. Department of Thoracic Surgery, Shaanxi Provincial Cancer Hospital Xi'an 710061, China.
3. Department of Medical Oncology, Shaanxi Provincial Cancer Hospital Xi'an 710061, China.
- Publication Type:Journal Article
- Keywords:
HIF-1α;
casticin;
non-small cell lung cancer;
proliferation;
reprogramming of glucose metabolism
- MeSH:
Humans;
Cell Proliferation/drug effects*;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*;
Carcinoma, Non-Small-Cell Lung/physiopathology*;
Lung Neoplasms/drug therapy*;
Glucose/metabolism*;
Cell Line, Tumor;
Glycolysis/drug effects*
- From:
China Journal of Chinese Materia Medica
2024;49(24):6755-6762
- CountryChina
- Language:Chinese
-
Abstract:
The study investigated the effect of casticin on the proliferation of non-small cell lung cancer(NSCLC) H322 cells and explored its molecular mechanism. Firstly, the cell counting kit-8(CCK-8) assay, colony formation assay, and EdU assay were used to detect the effect of casticin on the proliferation capacity of H322 cells under different concentrations and treatment durations. Then, glucose uptake, lactate production, extracellular pH, and oxygen consumption of H322 cells were measured before and after casticin treatment to analyze its impact on glycolysis in NSCLC H322 cells. Finally, real-time fluorescence quantitative PCR(RT-qPCR) and Western blot assays were performed to explore glycolysis-related molecules affected by casticin. The experiments showed that casticin inhibited the proliferation of NSCLC H322 cells in a dose-and time-dependent manner, with half-maximal inhibitory concentrations(IC_(50)) of 28.64 and 19.41 μmol·L~(-1) after 48 and 72 hours of treatment, respectively. Casticin also inhibited glucose uptake and lactate production in H322 cells, while increasing extracellular pH and oxygen consumption. Further investigation revealed that casticin inhibited the expression of glycolysis-related molecules, including glucose transporter 1(GLUT1), hexokinase 2(HK2), aldolase A(ALDOA), pyruvate kinase M2(PKM2), and hypoxia-inducible factor-1α(HIF-1α). Overexpression of HIF-1α was found to reverse the inhibitory effects of casticin on H322 cell proliferation and glycolysis. These findings suggest that casticin may regulate cellular glycolysis by inhibiting the expression of HIF-1α, thereby inhibiting the proliferation of NSCLC H322 cells. This study identifies a potential drug for the treatment of NSCLC and provides a direction for further research.
