RESUMEN
The biflavonoid isochamaejasmin is mainly distributed in the root of Stellera chamaejasme L. (Thymelaeaceae) that is used in traditional Chinese medicine (TCM) to treat tumors, tuberculosis, and psoriasis. Herein, isochamaejasmin was found to show similar bioactivity against Bcl-2 family proteins to the reference Bcl-2 ligand (-)-gossypol through 3D similarity search. It selectively bound to Bcl-xl and Mcl-1 with Ki values being 1.93 ± 0.13 μmol·L(-1) and 9.98 ± 0.21 μmol·L(-1), respectively. In addition, isochamaejasmin showed slight growth inhibitory activity against HL-60 with IC50 value being 50.40 ± 1.21 μmol·L(-1) and moderate growth inhibitory activity against K562 cells with IC50 value being 24.51 ± 1.62 μmol·L(-1). Furthermore, isochamaejasmin induced apoptosis of K562 cells by increasing the intracellular expression levels of proteins of the cleavage of caspase-9, caspase-3, and PARP which involved in the Bcl-2-induced apoptosis pathway. These results indicated that isochamaejasmin induces apoptosis in leukemia cells by inhibiting the activity of Bcl-2 family proteins, providing evidence for further studying the underlying anti-cancer mechanism of S. chamaejasme L.
Asunto(s)
Humanos , Antineoplásicos Fitogénicos , Farmacología , Usos Terapéuticos , Apoptosis , Biflavonoides , Farmacología , Usos Terapéuticos , Caspasa 3 , Metabolismo , Caspasa 9 , Metabolismo , Gosipol , Farmacología , Células HL-60 , Concentración 50 Inhibidora , Células K562 , Leucemia , Quimioterapia , Metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Metabolismo , Fitoterapia , Extractos Vegetales , Farmacología , Usos Terapéuticos , Poli(ADP-Ribosa) Polimerasas , Metabolismo , Proteínas Proto-Oncogénicas c-bcl-2 , Metabolismo , Transducción de Señal , Thymelaeaceae , Química , Proteína X Asociada a bcl-2 , MetabolismoRESUMEN
With the development of stem cells and regenerative medicine (treatment of various diseases using stem cells) research, the induction of differentiation of human stem cell technology has also made significant progress. The development of chemical biology offers a variety of small biological molecules for stem cell biology. This review focuses on how small molecule compounds (natural and synthetic) induce differentiation of stem cells.