Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells

Abstract

Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.

Anti-Gastric Cancer Activity of the Cell-free Culture Supernatant of Serofluid Dish and Lactiplantibacillus plantarum YT013

“…As is shown in Figure 4 , untreated cells showed that the nuclei were similar in size, and uniformly and lightly stained. Nevertheless, AGS cells treated with CCS2 at different concentrations showed typical morphological changes ( Ma et al, 2022 ), such as chromatin condensation, densely stained nuclei, and apoptotic bodies. These results suggested that apoptosis could be the potent mechanism of anti-proliferative activity.…”

Isolation, Identification, Anti-Inflammatory, and In Silico Analysis of New Lignans from the Resin of Ferula sinkiangensis

“…MGC-803, AGS, and HeLa cell lines were also purchased from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (Beijing, China). The cytotoxicities of the isolates were evaluated using a modified MTT assay [63]. AGS and HeLa cells were cultured in RPMI 1640 medium, while MGC-803 cells were cultured in DMEM, supplemented with 10% FBS.…”

Cytotoxic Indole Diterpenoids from a Sphagneticola trilobata-Derived Fungus Aspergillus sp. PQJ-1

“…Apoptosis, which occurs normally during development and aging, is a homeostatic mechanism for maintaining tissue cell populations and an important strategy for treating cancer [27]. Apoptosis leads to cell death with cell nuclear pyknosis and apoptotic body production, which was observed via fluorescence microscopy after Hoechst 33258 staining [27,28]. As shown in Figure 5A, untreated cells showed uniform blue fluorescence, but Hela cells treated with 1 for 48 h showed clear apoptotic signals, with shrinkage of chromatin, fragmentation of nuclei, and bright blue fluorescence, and apoptotic bodies appeared in apoptotic cells.…”

“…When the cells were walled and incubated for 48 h with different concentrations of the drug. The culture solution was aspirated and incubated with JC-1 staining solution for 20 min at 37 • C [28]. The supernatant was then aspirated and washed twice with JC-1 staining buffer before being observed under a fluorescence microscope and photographed.…”

“…Hela cells were inoculated in 24-well plates at 1 × 10 5 cells/well, and after walling, the cells were treated with compound 1 at concentrations of 0, 6.25, 12.50, 25.00 µM, respectively, and cultured for 48 h in an incubator at 37 • C [28]. The cells were washed twice with PBS, stained with Hoechst 33258 stain for 15 min, washed twice with PBS, and then photoprocessed with an OLYMPUS IX-51 fluorescence microscope.…”