Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition

Bioorg Med Chem. 2008 Jan 1;16(1):181-9. doi: 10.1016/j.bmc.2007.10.004. Epub 2007 Oct 5.

Abstract

Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticancer drug development. In this study, the MeOH soluble extract of Brazilian red propolis was found to kill 100% PANC-1 cells preferentially in the nutrient-deprived condition at the concentration of 10 microg/mL. Further phytochemical investigation led to the isolation of 43 compounds including three new compounds, (6aS,11aS)-6a-ethoxymedicarpan (1), 2-(2',4'-dihydroxyphenyl)-3-methyl-6-methoxybenzofuran (2), and 2,6-dihydroxy-2-[(4-hydroxyphenyl)methyl]-3-benzofuranone (3). Among them, (6aR,11aR)-3,8-dihydroxy-9-methoxypterocarpan (21, DMPC) displayed the most potent 100% preferential cytotoxicity (PC(100)) at the concentration of 12.5 microM. Further study on the mode of cell death induced by DMPC against PANC-1 cells indicated that killing process was not accompanied by DNA fragmentation, rather through a nonapoptotic pathway accompanied by necrotic-type morphological changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Necrosis / chemically induced
  • Nutritional Requirements
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology*
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Propolis / chemistry*
  • Propolis / therapeutic use*
  • Sensitivity and Specificity

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • Propolis