Mechanism of inhibiting proliferation of tumor cells by a new tetrahydroisoquinoline compound SYT-1
10.16438/j.0513-4870.2020-1298
- VernacularTitle:四氢异喹啉类新化合物SYT-1抑制肿瘤细胞增殖的机制
- Author:
Yu-yun LI
;
Wen-hui MA
;
Zhan-wei ZENG
;
Shi-yi LIAO
;
Yu-tong SUN
;
Yun-sheng HUANG
;
Dao-hua XU
- Publication Type:Research Article
- Keywords:
tetrahydroisoquinoline;
anti-tumor;
apoptosis;
monoclonal;
mitochondrial membrane potential
- From:
Acta Pharmaceutica Sinica
2021;56(1):217-223
- CountryChina
- Language:Chinese
-
Abstract:
In this study, we investigated the inhibitory effect of SYT-1, a new compound of tetrahydroisoquino-line, on tumor cell proliferation and underlying mechanisms. Cell counting kit-8 (CCK-8) method was used to detect cell proliferation; clone formation experiment was used to detect cell clone formation ability; JC-1 probe was used to detect cell mitochondrial membrane potential; 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe was used to detect intracellular reactive oxygen species; Annexin V-FITC/PI (fluorescein isothiocyanate/propidium) counterstaining method was used to detect apoptosis; Western blot assay was used to detect the expression level of related proteins. The experimental results show that SYT-1 has a significant inhibitory effect on the proliferation of six human-derived cancer cells. Among them, the inhibitory effect on breast cancer MCF-7 cells is the strongest, the half maximal inhibitory concentration (IC50) of SYT-1 of 48 h administration on MCF-7 cells is 5.87 μmol·L-1, which is better than that of cisplatin (8.92 μmol·L-1). Further studies have shown that SYT-1 can dose-dependently inhibit the monoclonal formation ability of MCF-7 cells, and can cause the mitochondrial membrane potential of the cells to decrease and the level of reactive oxygen species to increase. In addition, SYT-1 can significantly inhibit the activation of PI3K-Akt (phosphatidylinositol 3-kinase/protein kinase B) signaling pathway and induce apoptosis of MCF-7 cells. The above research results show that, as a new type of tetrahydroisoquinoline compound, SYT-1 has the potential to inhibit tumor cell proliferation.
