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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.

The study aimed to analyze the potency of Cyperus rotundus bioactive compounds to inhibit the anti-apoptotic protein Bcl-2 and Bcl-xl by in silico approach. Ten bioactive compounds were used in this study, such as apigenin, aureusidin, cyperol, cyperusol A1, cyperusol B2, cyperusol D, luteolin, methyltartonic, quercetin, and scaberin. The 3D structure of ligands and protein was retrieved from PubChem and Protein Data Bank (www.rscb.org). The molecular docking analysis was done by AutoDock Vina in PyRx v.0.8. The results showed that the lowest binding affinity against bcl-2 was obatoclax as control ligand and followed by scaberin, aureusidin, luteolin, apigenin, and quercetin with binding affinity score - 7.4, -7, -6.9, -6.9, and -6.8 kcal/mol, respectively. Those ligands also found have the best binding affinity against Bcl-xl where apigenin, luteolin, and quercetin were -8 kcal/mol and lower than the binding affinity of obatoclax, aureusidin, and scaberin (-7.8, -7.8, and -7.3 kcal/mol, respectively). Based on the prediction of cytotoxic potential of drug-like compounds using Pass program showed the best cytotoxic activity of obatoclax against HT-29 cell line (pa>0.6), apigenin against Hs 683 (pa>0.5), luteolin against Hs 683 (pa>0.5), and quercetin against CWR22R (pa>0.5). In conclusion, the bioactive compounds of Cyperus rotundus exhibited a potential anti-cancer activity through the inhibition of Bcl-2 and Bcl-xl. Further study needs to justify the anti-cancer mechanism of Cyperus rotundus extract.

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Context: Aerobic glycolysis is a breast cancer hallmark that has become a novel target for anticancer therapy. GLUT1, HK2, PKM2, and LDHA are oncogenic proteins in the pathway. The compounds of ethyl acetate fraction of Selaginella doederleinii Hieron extract can be developed as aerobic glycolysis inhibitors by impeding the proteins’ activity. Aims: To analyze the anticancer activity of compounds of the ethyl acetate fraction of S. doederleinii via inhibiting oncogenic proteins in the aerobic glycolysis pathway. Methods: The 3D protein structures were obtained from the RCSB database. Ligands were compounds of the ethyl acetate fraction predicted to have a good oral bioavailability based on our previous study. The ligand structures were downloaded from the PubChem database. Docking and analysis of chemical interactions were performed using Autodock Vina in Pyrx and Discovery Studio 2020, respectively. Results: Some compounds interacted with the specific binding site of proteins with low binding affinity. Diosgenin interacted with GLUT1 and LDHA with the binding affinity of -11.8 and -9.6 kcal/mol. Frutinone A was found to bind PKM2 and LDHA with the binding affinity of -10.0 and -8.4 kcal/mol. Vitexin interacted with GLUT1 and PKM2 with the binding affinity of -10.4 and -10.0 kcal/mol. Valerodine and 5-hydroxyferulic acid methyl ester could bind HK2 with a binding affinity of -6.1 and -6.8 kcal/mol. Conclusions: The compounds of ethyl acetate fraction of S. doederleinii extract were predicted to inhibit GLUT1, HK2, PKM2, and LDHA. Therefore, these compounds could be developed as anti-breast cancer agents targeting the aerobic glycolysis pathway.