2. Academic Validation
  3. Cytotoxic effects of the biflavonoids isolated from Selaginella trichoclada on MCF-7 cells and its potential mechanism

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.
Yang Xie 1,  Xi Zhou 2,  Jing Li 3,  Xiao-Chang Yao 3,  Wan-Li Liu 3,  Ping-Sheng Xu 3,  Gui-Shan Tan 4
Affiliations

Affiliations

  • 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: xiey11105@163.com.
  • 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: tgs395@csu.edu.cn.
PMID: 34875389 DOI: 10.1016/j.bmcl.2021.128486
Abstract

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.

Keywords

Breast cancer; Ochnaflavone; Robustaflavone; Selaginella.

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