Cytotoxic activities of Amaryllidaceae alkaloids against gastrointestinal cancer cells

  • Doskočil I
  • Hoš͗álková A
  • Šafratová M
 et al. 
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Abstract

Abstract The treatment of many diseases is highly dependent on natural products and natural products can also be used as design templates for future anticancer drugs. Thirteen Amaryllidaceae alkaloids possessing α-crinane, β-crinane, galantamine, lycorine and tazettine-type skeleton have been isolated in our laboratory, and their cytotoxicity against p53-mutated gastrointestinal cancer cells were evaluated. At the same time, healthy small intestine cells were used to determine overall toxicity against noncancerous cells. In this study, we demonstrated that haemanthamine, haemanthidine and lycorine showed strong cytotoxicity against p53-mutated Caco-2 and HT-29 colorectal adenocarcinoma cells as quantified in terms of IC50 values. We for the first time observed approximately 20 times higher IC50values against normal intestine epithelial cells FHs-74 Int after haemanthamine and lycorine treatment when compared with Caco-2 and HT-29 cancer cells. In conclusion, our data indicate that α-C2 bridged haemanthamine may be perspective anticancer drug candidate for further semisynthetic modification and structure-activity relationship study.

Author-supplied keywords

  • Amaryllidaceae
  • Caco-2
  • Cytotoxicity
  • FHs 74 Int
  • HT-29
  • Haemanthamine

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