Over-expression of survivin is a factor responsible for differential responses of ovarian cancer cells to S-allylmercaptocysteine (SAMC)

Exp Mol Pathol. 2016 Apr;100(2):294-302. doi: 10.1016/j.yexmp.2016.02.003. Epub 2016 Feb 16.

Abstract

While investigating the inhibitory effect of S-allylmercaptocysteine (SAMC), a garlic derivative, on ovarian cancer, we subjected three ovarian cancer cell lines, HO8910, HO8910PM, and SKOV3, to SAMC treatment. In vivo and in vitro experiments showed that only HO8910 and SKOV3 cells were highly sensitive to SAMC, whereas HO8910PM cells were resistant to SAMC. Subsequently, we examined the apoptosis-related genes in the three cell lines. We found that survivin gene was highly expressed in HO8910PM cells. Down regulation of survivin gene in HO8910PM cells with small interference RNA (siRNA), resulted in increased sensitivity to SAMC together with a decrease in invasiveness of tumor cells. We therefore concluded that the S-allylmercaptocysteine suppresses both the proliferation and distant metastasis of epithelial ovarian cancer cells, insensitivity of HO8910PM cells to SAMC was closely related to the high level of survivin expression and that combination of SAMC treatment together with survivin knockdown might be a potential strategy for treatment of certain variants of ovarian cancers.

Keywords: Drug resistance; E-cadherin; Integrin β1; Ovarian cancer; S-allylmercaptocysteine; Surviving.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Blotting, Western
  • Cadherins / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacology
  • Female
  • Garlic / chemistry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Integrin beta1 / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Cadherins
  • Inhibitor of Apoptosis Proteins
  • Integrin beta1
  • S-allylmercaptocysteine
  • Survivin
  • Caspase 3
  • Cysteine