Chemical characterization of cytotoxic indole acetic acid derivative from mulberry fruit (Morus alba L.) against human cervical cancer

Bioorg Chem. 2018 Feb:76:28-36. doi: 10.1016/j.bioorg.2017.10.015. Epub 2017 Nov 7.

Abstract

The fruit of the white mulberry tree (Morus alba L.) is a multiple fruit with a sweet flavor commonly consumed around the world. Chemical investigation of the fruits led to the isolation of two indole acetic acid derivatives (1 -2) including a new compound, which turned out to be an isolation artifact, 3S-(β-D-glucopyranosyloxy)-2,3-dihydro-2-oxo-1H-indole-3-acetic acid butyl ester (1), along with five known compounds (3 -7). Compounds 2 and 7 were newly identified from mulberry fruit. The new isolation artifact (1) exhibited cytotoxic effect on human cervical cancer Hela cells in a dose-dependent manner. Compound 1 activated caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of caspase-3, in a dose-dependent manner. Simultaneous alterations in protein expression of mitochondrial factors Bax, BID and Bcl-2 were also observed. A comparison between compounds 1 and 2 led to a structure-activity relationship analysis of the cytotoxic effect. These results suggest that compound 1 could be beneficial in human cervical cancer treatment, and provide a theoretical basis for further application of compound 1.

Keywords: Human cervical cancer; Indole acetic acid; Morus alba; Mulberry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Female
  • Fruit / chemistry
  • Glucosides / chemistry
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • HeLa Cells
  • Humans
  • Indoleacetic Acids / chemistry
  • Indoleacetic Acids / isolation & purification
  • Indoleacetic Acids / pharmacology*
  • Morus / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Uterine Cervical Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Glucosides
  • Indoleacetic Acids
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9