title: Interaction studies of an anticancer alkaloid, (+)-(13aS)-deoxytylophorinine, with calf thymus DNA and four repeated double-helical DNAs.
abstract: BACKGROUND
  Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity. The specific biomolecular targets of these alkaloids have not yet been clearly identified. (+)-(13aS)-deoxytylophorinine is a new phenanthroindolizidine alkaloid originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata in our institute. (+)-(13aS)-deoxytylophorinine exerts both in vitro and in vivoanticancer activities.
  
  
  METHODS
  The in vivo anticancer effects and toxicity of this compound were investigated in mice, and interactions between this compound and double-helical DNA sequences were studied in detail with circular dichroic spectroscopy and fluorescence spectroscopy. Viscosity measurements were applied to check the interactive mode between this compound and DNA.
  
  
  RESULTS
  Potent anticancer effects were observed in vivo. Also, concentration-dependent interactions were observed and this compound seemed to interact in a sequence-specific manner with AT-repeated sequences of double-helical DNA. Such interactions were proved to be intercalating by viscosity measurements.
  
  
  CONCLUSIONS
  Anticancer alkaloid (+)-(13aS)-deoxytylophorinine can have sequence-specific interactions with DNA in an intercalating manner.
authors: Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors: Zhenjia
authors: Z
authors: Liu
authors: Haining
authors: H
authors: Lv
authors: Hongyan
authors: H
authors: Li
authors: Yi
authors: Y
authors: Zhang
authors: Haijing
authors: H
authors: Zhang
authors: Fuqin
authors: F
authors: Su
authors: Song
authors: S
authors: Xu
authors: Yong
authors: Y
authors: Li
authors: Yikang
authors: Y
authors: Si
authors: Shishan
authors: S
authors: Yu
authors: Xiaoguang
authors: X
authors: Chen
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D054836:Indolizidines / Q000737:chemistry* / Q000494:pharmacology*; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D009690:Nucleic Acid Conformation; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D031110:Tylophora / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C569808:(13aS)-deoxytylophorinine; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D054836:Indolizidines; D007364:Intercalating Agents; D010618:Phenanthrolines; D004247:DNA; C427203:calf thymus DNA