title: Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells.
abstract: BACKGROUND
  Melanomas are aggressive neoplasms with limited therapeutic options. Therefore, developing new therapies with low toxicity is of utmost importance. Honokiol is a natural compound that recently has shown promise as an effective anticancer agent.
  
  
  METHODS
  The effect of honokiol on melanoma cancer cells was assessed in vitro. Proliferation and physiologic changes were determined using hexosaminidase assay and transmission electron microscopy. Protein expression was assessed by immunoblotting.
  
  
  RESULTS
  Honokiol treatment inhibited cell proliferation and induced death. Electron microscopy showed autophagosome formation. Reduced levels of cyclin D1 accompanied cell-cycle arrest. Honokiol also decreased phosphorylation of AKT (known as protein kinase B) and mammalian target of rapamycin, and inhibited γ-secretase activity by down-regulating the expression of γ-secretase complex proteins, especially anterior pharynx-defective 1.
  
  
  CONCLUSIONS
  Honokiol is highly effective in inhibiting melanoma cancer cells by attenuating AKT/mammalian target of rapamycin and Notch signaling. These studies warrant further clinical evaluation for honokiol alone or with present chemotherapeutic regimens for the treatment of melanomas.
authors.affiliation: Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaushik
authors.forename: Satish
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Dharmalingam
authors.initials: D
authors.lastname: Subramaniam
authors.forename: Parthasarthy
authors.initials: P
authors.lastname: Rangarajan
authors.forename: Piero
authors.initials: P
authors.lastname: Protti
authors.forename: Prabhu
authors.initials: P
authors.lastname: Rammamoorthy
authors.forename: Shrikant
authors.initials: S
authors.lastname: Anant
authors.forename: Joshua M V
authors.initials: JM
authors.lastname: Mammen
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015151:Immunoblotting; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D053829:Amyloid Precursor Protein Secretases; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D001713:Biphenyl Compounds; D019938:Cyclin D1; D017705:Lignans; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C530105:Ccnd1 protein, mouse; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C546843:mTOR protein, mouse