Biflavonoid compounds from Selaginella doederleinii Hieron as anticancer agents of hormone receptor-positive (HR+) breast cancer based on in silico study

Selaginella doederleinii Hieron is a wild plant that has long been used as a traditional anticancer drug in Indonesia. The majority of its anticancer activity comes from biflavonoids. However, the potency of the biflavonoids as anticancer agents for hormone receptor-positive (HR+) breast cancer, the most common type of cancer in Indonesia has never been identified. This study determined the potential of the biflavonoids to block ERα and CDK6 via molecular docking and identified the interactions of the two proteins with other oncogenic proteins via protein interaction network analysis. The results showed that 3',3'''-binaringenin, Hinokiflavone, and 2,3-dyhidrohinokiflavone were the most potent compounds as ERα inhibitor. Hinokiflavone and Amentoflavone were the two best compounds that could inhibit CDK6 according to their high binding affinity. The presence of amino acid residues is vital in the binding process and the significant similarity with commercial drugs. ERα could interact with NCOA1, NCOA2, PELP1, CCND1, and AKT1, whereas CDK6 interacted directly with CCND1, CCND2, and CCND3. The upregulation of these proteins relates to the increase in cancer proliferation. These data indicated that the biflavonoids had a promising anticancer effect on HR+ breast cancer based on in silico studies. Additional researches are needed to validate the results.