Effects of a new synthetic zerumbone pendant derivative (ZPD) on apoptosis induction and anti-migratory effects in human cervical cancer cells

Chem Biol Interact. 2017 Dec 25:278:32-39. doi: 10.1016/j.cbi.2017.10.006. Epub 2017 Oct 5.

Abstract

A newly synthesised zerumbone pendant derivative (ZPD) was studied in human cervical cancer cells (HeLa) for its anticancer properties. ZPD significantly inhibited the growth of human cervical cancer cells with a GI50 value of 6.35 ± 1.30 μM, which also induced morphological changes and apoptosis in a dose-dependent manner. Our data indicated that ZPD actively encouraged programmed cell death in HeLa cells which were confirmed by DNA fragmentation, phosphatidylserine translocation, increased activity of caspase 3, upregulation of the expression of the pro-apoptotic protein Bax, cleaved PARP, cleaved caspase 3 and downregulation of anti-apoptotic protein Bcl-2. ZPD also inhibited cell migration of HeLa cells, decreasing the production of MMP-2,-9 and downregulation of expression of MMPs and pro-angiogenic factor VEGF. Also it is nontoxic to normal rat cardiac myoblasts. Overall, ZPD is a promising candidate for inducing cytotoxicity, apoptosis and anti-migratory effects in cervical cancer cells.

Keywords: Apoptosis; Cell migration; HeLa cells; Zerumbone; Zingiber zerumbet.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Movement / drug effects
  • DNA Fragmentation / drug effects
  • Down-Regulation / drug effects
  • Female
  • HeLa Cells
  • Humans
  • Microscopy, Fluorescence
  • Paclitaxel / toxicity
  • Phosphatidylserines / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Up-Regulation / drug effects
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Phosphatidylserines
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • bcl-2-Associated X Protein
  • zerumbone
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Paclitaxel