Cytotoxic constituents from Celastrus paniculatus induce apoptosis and autophagy in breast cancer cells

Phytochemistry. 2013 Oct;94:211-9. doi: 10.1016/j.phytochem.2013.05.022. Epub 2013 Jun 27.

Abstract

Celastrus paniculatus is a traditional medicinal plant with diverse pharmacological activities. To identify its bioactive constituents, three new β-dihydroagarofuranoid sesquiterpenes were isolated from the whole plant, of which the major constituent is (1α,2α,8β,9β)-1,8-bis(acetyloxy)-2,9-bis(benzoyloxy)-14-hydroxy-β-dihydroagarofuran. It was assessed for its antiproliferative activity, and it suppressed the viability of MCF-7 breast cancer cells with an IC50 of 17±1μM. This growth inhibition was, in part, attributable to apoptosis. Moreover, this drug treatment led to LC3B-II accumulation, indicative of autophagy. Western blot analysis established its ability to target a broad range of signaling effectors related to survival and cell cycle progression, including Akt, NF-κB, p53, and MAP kinases. In addition, flow cytometry analysis indicates increased reactive oxygen species production in response to this compound. Taken together, these findings suggest a pleiotropic mode of mechanism that underlies the antiproliferative activity of this compound in MCF-7 breast cancer cells.

Keywords: 4,6-diamidino-2-phenylindole; Apoptosis; Autophagy; CDK; Celastraceae; Celastrus paniculatus; DAPI; DMSO; ECL; ERK; FBS; LC3B; MAP kinases; PARP; PBS; SDS; Sesquiterpenes; cyclin-dependent kinase; dimethylsulfoxide; enhanced chemiluminescence; extracellular signal-regulated kinases; fetal bovine serum; microtubule-associated protein 1 light chain 3B; mitogen-activated protein kinases; phosphate buffered saline; poly ADP-ribose polymerase; sodium lauryl sulfate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Celastrus / chemistry*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Structure
  • NF-kappa B / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • (1alpha,2alpha,8beta,9beta)-1,8-bis(acetyloxy)-2,9-bis(benzoyloxy)-14-hydroxy-beta-dihydroagarofuran
  • Antineoplastic Agents, Phytogenic
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • NF-kappa B
  • Plant Extracts
  • Reactive Oxygen Species
  • Sesquiterpenes
  • Tumor Suppressor Protein p53
  • dihydroagarofuran
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases