title: Isochamaejasmin induces apoptosis in leukemia cells through inhibiting Bcl-2 family proteins.
abstract: 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.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Shou-De
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.affiliation: Qinghai Academy of Agriculture and Forestry Science, Xining 810016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: hlli@ecust.edu.cn.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: wdzhangy@hotmail.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D044946:Biflavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D006072:Gossypol / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D029645:Thymelaeaceae / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044946:Biflavonoids; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C507044:isochamaejasmin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D006072:Gossypol
keywords: (−)-Gossypol; 3D Similarity search; Apoptosis; Bcl-2; Isochamaejasmin; Stellera chamaejasme L.