23,24-Dihydrocucurbitacin B induces G2/M cell-cycle arrest and mitochondria-dependent apoptosis in human breast cancer cells (Bcap37)

Cancer Lett. 2007 Oct 28;256(2):267-78. doi: 10.1016/j.canlet.2007.06.018. Epub 2007 Aug 6.

Abstract

23,24-Dihydrocucurbitacin B (DHCB), a cucurbitacin-derived compound known to posses anticancer and anti-inflammatory activities. In this study, DHCB, isolated from roots of Trichosanthes kirilowli which is a traditional Chinese herb medicine used as treatments for cancer and other diseases, has been found to inhibit the proliferation of human cancer cell lines Bcap37, HeLa, SW620, SMMC-7721, K562 and MCF-7 in a dose- and time-dependent manner, and induce apoptosis in human breast cancer cell line Bcap37 at low concentration. DHCB-induced Bcap37 apoptosis was characterized with the changes in nuclear morphology, DNA fragmentation, activation of caspase-like activities, poly(ADP-ribose) polymerase cleavage, release of cytochrome c into cytosol. The cell death was partly prevented by a caspase-family inhibitor Z-VAD-FMK. The results suggest that DHCB-induced Bcap37 apoptosis through mitochondrial dependent pathway. Flow cytometric analysis revealed that at the lower dose of 1.8 and 3.6muM, DHCB-induced cancer cell lines death via an apoptotic process rather than necrotic one; whereas, the higher dose of 8.9, 17.9 and 35.7muM induced cell death via the necrotic process. Cell-cycle analysis demonstrated DHCB induction of G(2)/M phase cell-cycle arrest and apoptosis. The overall results suggest that DHCB might have the therapeutic value against human cancer cell lines, especially the breast cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspases / metabolism
  • Cell Division / drug effects*
  • Cell Membrane / drug effects
  • Cell Membrane / pathology
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytochromes c / metabolism
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Female
  • G2 Phase / drug effects*
  • HeLa Cells
  • Humans
  • K562 Cells
  • Mitochondria / drug effects*
  • Mitochondria / pathology
  • Necrosis
  • Plant Roots
  • Poly(ADP-ribose) Polymerases / metabolism
  • Trichosanthes* / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use

Substances

  • Amino Acid Chloromethyl Ketones
  • Antineoplastic Agents, Phytogenic
  • Cysteine Proteinase Inhibitors
  • Triterpenes
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • 23,24-dihydrocucurbitacin B