title: Methylenedioxy flavonoids: assessment of cytotoxic and anti-cancer potential in human leukemia cells.
abstract: A new series of chalcones, flavanones and flavones with methylenedioxy group at the 3',4' position in chalcone, 7,8 position in flavanones and flavones with mono-, di- and trimethoxy groups in the benzaldehyde ring have been assessed for their effect on proliferation, cytotoxic potential and apoptosis in human leukemia cells. Among the tested compounds, the chalcone series showed the best activity and chalcone 3 (mono methoxy group at the ortho position in A-ring) showed a significant effect on down-regulation of cancer cell proliferation and viability in three different leukemia cell lines (K562, Jurkat, U937). The executioner caspase cleavage analyses indicated that the cytotoxic effect mediated by chalcone 3 is due to induction of apoptotic cell death. Interestingly, the cytotoxic effect was cell type-specific and targeted preferentially cancer cells as peripheral blood mononuclear cells (PBMCs) from healthy donors were less affected by the treatment compared to K562, Jurkat and U937 leukemia cells. Altogether our results indicate a potential drug candidate with interesting differential toxicity obeying Lipinski's rule of five.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea; Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg.
authors.forename: Barbora
authors.initials: B
authors.lastname: Orlikova
authors.affiliation: Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal; Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India.
authors.forename: José C J M D S
authors.initials: JC
authors.lastname: Menezes
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea.
authors.forename: Seungwon
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India.
authors.forename: Shrivallabh P
authors.initials: SP
authors.lastname: Kamat
authors.affiliation: Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: José A S
authors.initials: JA
authors.lastname: Cavaleiro
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea. Electronic address: marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D005419:Flavonoids
keywords: Anti-inflammatory; Chalcones; Cytotoxic; Flavanones; Flavones; Leukemia