Cytotoxic effects of the biflavonoids isolated from Selaginella trichoclada on MCF-7 cells and its potential mechanism
- Bioorg Med Chem Lett. 2022 Jan 15:56:128486. doi: 10.1016/j.bmcl.2021.128486.
- 1. Department of Orthopedics, Xiangya Hospital, Central South University, PR China; Phase I Clinical Trial Center, Xiangya Hospital, Central South University, PR China. Electronic address: [email protected].
- 2. School of Life Sciences, Central South University, PR China.
- 3. Phase I Clinical Trial Center, Xiangya Hospital, Central South University, PR China.
- 4. Phase I Clinical Trial Center, Xiangya Hospital, Central South University, PR China. Electronic address: [email protected].
A new biflavonoid, (2''S)-6''-methyl-2'',3''-dihydroochnaflavone (1), along with two known ochnaflavones (2, 3), four known amentoflavones (4-7) and two known robustaflavones (8, 9) were obtained from the 70% EtOH extract of Selaginella trichoclada. The chemical structures of isolated compounds were elucidated by extensive spectroscopic analyses. Overall, compounds 1-9 displayed moderate cytotoxic effects against human breast Cancer MCF-7 cell lines. Among them, compounds 2 and 8 exhibited relatively strong cytotoxic effects against MCF-7 cells with an IC50 value of 7.7 and 6.9 μΜ, respectively. The results of RNA-sequencing and KEGG functional enrichment analysis showed that 8 could induce Ferroptosis in MCF-7 cells by down-regulating the expression of ferroptosis-related genes including ACSL4, NOXO1, NOXA1, ACSL5, STEAP3, LPCAT3, Atg7 and TP53. Then 8 could inhibit the expression of ACSL4 proteins through molecule docking analysis, which showed a strong interaction of - 11.89 Kcal/mol binding energy. Those results indicate that 8 could be chemotherapy agents to fight drug resistance in breast Cancer by down-regulating the expression level of ACSL4 proteins via Ferroptosis, which needs to be further certified in vitro.