title: Wogonin induces apoptosis in RPMI 8226, a human myeloma cell line, by downregulating phospho-Akt and overexpressing Bax.
abstract: OBJECTIVE
  Wogonin is one of the major constituents derived from Scutellaria Baicalensis, which has been reported to inhibit cell growth and/or induce apoptosis in various cancer cell lines. We aim to investigate the anticancer effects and associated mechanisms of wogonin on human multiple myeloma cell line in vitro.
  
  
  METHODS
  Effects of wogonin on the proliferation, cell cycle progression, and apoptosis of human myeloma cells were examined in vitro. The proteins associated with the biological effects of wogonin were analyzed by immunoblotting and immunocytochemical staining. In addition, the binding mode of wogonin within crystal structure of Akt1 protein was also evaluated by molecular docking analysis using the CDOCKER algorithm in Discovery Studio.
  
  
  RESULTS
  Myeloma cell growth was attenuated by wogonin (70.4-352.0 μM) in a concentration-dependent manner. Cell cycle progression analysis and TUNEL assay showed that apoptosis was enhanced in wogonin-treated cells. Increased apoptosis was accompanied by decreased level of total-PARP, the arisen of PARP cleavage, significantly increased level of Bax protein and decreased level of Bcl-2 protein. Akt activity was suppressed and phosphorylation of Ser 473 residue was decreased in the wogonin-treated cells. Molecular docking analysis revealed wogonin could be stably docked into the ligand binding domain of Akt1 protein, and presented unique features of binding to Akt1, which indicated detailed interaction between wogonin and Akt signaling pathway.
  
  
  CONCLUSIONS
  As wogonin was effective in vitro in promotion of apoptosis of myeloma cell by Akt-modulated, Bax and Bcl-2 related intrinsic apoptotic pathway, wogonin may be a potential therapeutic agent against multiple myeloma.
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, 58, Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liu
authors.forename: Yuling
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiao-ying
authors.initials: XY
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Sui-Lin
authors.initials: SL
authors.lastname: Mo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D044950:Flavanones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D062105:Molecular Docking Simulation; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D031364:Scutellaria baicalensis / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; C085514:wogonin