The Hexane Fraction of Bursera microphylla A. Gray Induces p21-Mediated Anti-Proliferative and Pro-Apoptotic Effects in Human Cancer-Derived Cell Lines

Integr Cancer Ther. 2018 Mar;17(1):138-147. doi: 10.1177/1534735417696721. Epub 2017 Mar 9.

Abstract

Bursera microphylla (BM), one of the common elephant trees, is widely distributed in the Sonoran Desert in Mexico. The Seri ethnic group in the Sonoran Desert uses BM as an anti-inflammatory and painkiller drug for the treatment of sore throat, herpes labialis, abscessed tooth, and wound healing. Dried stems and leaves of BM are used in a tea to relieve painful urination and to stimulate bronchial secretion. Furthermore, BM is used for fighting venereal diseases. To investigate the effects of the hexane fraction of resin methanol extract (BM-H) on cell growth, the acute myeloid cell line (OCI-AML3) was treated with 250, 25, or 2.5 µg/mL of BM-H. The first 2 concentrations were able to significantly decrease OCI-AML3 cell number. This reduced cell number was associated with decreased S-phase, blockade of the G2/M phase of the cell cycle, and increased cell death. Similar results were obtained on all tested tumor cell lines of different origins. We found that blockade of the cell cycle was due to upregulation of p21 protein in a p53-independent way. Increase of p21 was possibly due to upstream upregulation of p-ERK (which stabilizes p21 protein) and downregulation of p-38 (which promotes its degradation). Regarding cell death, activation of caspase-3, but not of caspase-8 or -9, was detectable after BM-H treatment. In conclusion, these data suggest that the BM's hexane fraction inhibited proliferation of cell lines mainly by a p21-dependent, p53-independent mechanism and promoted apoptosis through activation of caspase-3, but not caspase-8 or -9.

Keywords: Bursera microphylla A. Gray; Mexican traditional medicine; anti-proliferative effect; human cancer cell lines; p21; pro-apoptotic effect.

Publication types

  • Duplicate Publication
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Apoptosis / drug effects*
  • Bursera / chemistry*
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • HCT116 Cells
  • HL-60 Cells
  • Hexanes / chemistry
  • Humans
  • Jurkat Cells
  • K562 Cells
  • MCF-7 Cells
  • Plant Extracts / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism
  • U937 Cells

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Hexanes
  • Plant Extracts
  • Tumor Suppressor Protein p53
  • Caspase 3