Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells

Molecules. 2021 Apr 21;26(9):2422. doi: 10.3390/molecules26092422.

Abstract

Cytotoxicity and apoptosis-inducing properties of compounds isolated from Garcinia subelliptica leaves were investigated. The hexane-soluble portion of MeOH extracts of G. subelliptica leaves that showed cytotoxic activity was separated to yield seven compounds 1-7. Chemical structure analysis using NMR spectroscopy and mass spectrometry confirmed that compound 1 was canophyllol, and compounds 2-7 were garcinielliptones N, O, J, G, F, and garcinielliptin oxide, respectively. Among them, garcinielliptone G (5) showed growth inhibition by causing apoptosis in THP-1 and Jurkat cells derived from human acute monocytic leukemia and T lymphocyte cells, respectively. Apoptosis induced by garcinielliptone G (5) was demonstrated by the detection of early apoptotic cells with fluorescein-labeled Annexin V and increases in cleaved caspase-3 and cleaved PARP protein levels. However, the addition of caspase inhibitor Z-VAD-FMK did not affect growth arrest or apoptosis induction. These results suggest that garcinielliptone G (5) can induce both caspase-3 activation and caspase-independent apoptosis. Therefore, garcinielliptone G (5) may be a potential candidate for acute leukemia treatment.

Keywords: Garcinia subelliptica; apoptosis; garcinielliptone G; human acute leukemia cell lines.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Garcinia / chemistry*
  • Humans
  • Jurkat Cells
  • Leukemia
  • THP-1 Cells
  • Triterpenes / chemistry*
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Triterpenes
  • garcinielliptone
  • Caspases