Exploring the potential of baicalin and resveratrol as PIM-1 kinase inhibitors: Therapeutic targeting of prostate and breast cancers

PIM-1 kinase is a member of the Ser/Thr kinases family, a well-studied therapeutic target for cancer therapy. The overexpression of PIM-1 is associated with prostate and breast cancer progression. Therapeutic targeting of PIM1 disrupts crucial signaling pathways which contributes to cancer growth and resistance to conventional treatments. Here, we screened 100 natural compounds with known antioxidant properties to discover potential inhibitors of PIM-1. Two natural compounds, baicalin, and resveratrol, were investigated for their binding affinity and PIM-1 inhibitory potential using integrated computational and experimental approaches. Baicalin and resveratrol bind to PIM-1 with a docking score of -10.2 and -7.5 kcal/mol, respectively. Subsequently, fluorescence binding studies showed an excellent affinity with Ka values, 5.9 x 105 M-1 and 1.7 x 107 M-1 for baicalin and resveratrol, respectively. In addition, baicalin and resveratrol strongly inhibited the kinase activity of PIM-1 with IC50 values of 36.8 mu M and 75 mu M, respectively. Furthermore, both baicalin and resveratrol suppress the proliferation of cancer cells in a dose-dependent manner, with baicalin's IC50 value for LNCaP and MDA-MB-231 cells being 34.8 mu M and 35.6 mu M, respectively, and resveratrol's being 15.2 mu M and 41.6 mu M, respectively. We conclude that baicalin and resveratrol may be considered potent PIM-1 inhibitors, opening promising possibilities for the development of anti-cancer therapy via targeting PIM-1 for prostate and breast cancer. Finally, utilizing natural compounds that offer a safer alternative to drive the development of more potent, specific, and pharmacokinetically optimized derivatives for therapeutic targeting of emerging diseases.