title: The nanoparticulate Quillaja saponin KGI exerts anti-proliferative effects by down-regulation of cell cycle molecules in U937 and HL-60 human leukemia cells.
abstract: Cancer cells are characterized by uncontrolled replication involving loss of control of cyclin dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, which is a nanoparticle with a Quillaja saponin as an active molecule. By the use of RNA array analysis and confirmation at the protein level, we show that KGI affects myeloid leukemia cells (in particular, the U937 monoblast cancer cell) by the following mechanisms: (A) ceasing cell replication via proteasome degradation, (B) down-regulation of key molecules at check points between G1/S and G2/M phases, (C) reduction of thymidine kinase activity, followed by (D) exit to differentiation and production of interleukin-8 (IL-8), eventually leading to apoptosis. Leukemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Thus our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukemic cells by interfering with the cell cycle process.
authors.affiliation: Duecom AB , Uppsala , Sweden.
authors.forename: Saideh
authors.initials: S
authors.lastname: Berenjian
authors.forename: Kefei
authors.initials: K
authors.lastname: Hu
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Abedi-Valugerdi
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.forename: Sadia
authors.initials: S
authors.lastname: Bashir Hassan
authors.forename: Bror
authors.initials: B
authors.lastname: Morein
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011687:Purines / Q000494:pharmacology; D062605:Quillaja Saponins / Q000737:chemistry*; D000077546:Roscovitine; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D011687:Purines; D062605:Quillaja Saponins; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases
keywords: CDK; Nanoparticle; apoptosis; cell cycle; cyclin; differentiation