Association of Sp1 and survivin in epithelial ovarian cancer

Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation

Umesh Tanaji Sankpal, Susan B. Ingersoll, Sarfraz Ahmad, Robert W. Holloway, Vadiraja B. Bhat, Jerry Simecka, Liz Daniel, Ekamber Kariali, Jamboor K. Vishwanatha, Riyaz Mahammad Basha

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

The expression of specificity protein 1 (Sp1) and survivin was evaluated in clinical specimens of epithelial ovarian cancer (EOC) patients. When compared to normal tissue, EOC samples showed high expression of Sp1 and survivin using qPCR (Sp1: ∼2-fold; survivin: ∼5-fold) and Western blot (Sp1: >2.6-fold; survivin: >100-fold). The Sp1 inhibitor, and anti-cancer small molecule, tolfenamic acid (TA), was tested to enhance the response of Cisplatin (Cis) in EOC cell lines. Cell viability (CellTiter-Glo), combination index (CalcuSyn software), apoptosis (Annexin-V staining), cell cycle analyses (flow cytometry), and reactive oxygen species (flow cytometry) were determined. Cell migration and invasion was assessed using matrigel coated transwell chambers. Agilent Technologies proteomics analysis identified potential signaling pathways involved. The combination of TA (50 μM) and Cis (5 μM) synergistically increased the growth inhibition in ES2 (∼80 %, p < 0.001) and OVCAR-3 (60 %, p < 0.001) cells. TA or TA + Cis treatment in ES2 cells caused cell cycle arrest in G1 Phase (TA) or S-Phase (TA + Cis) and unregulated reactive oxygen species. Invasion and migration was decreased in ES2 cells. Global proteomic profiling showed modulation of proteins associated with oxidative phosphorylation, apoptosis, electron transport chain, DNA damage, and cell cycle proteins. These results demonstrate an association of Sp1 and survivin in EOC and confirm targeting these candidates with TA potentially sensitizes EOC cells to cisplatin.

Original languageEnglish
Pages (from-to)14259-14269
Number of pages11
JournalTumor Biology
Volume37
Issue number10
DOIs
StatePublished - 1 Oct 2016

Fingerprint

Cisplatin
Cell Proliferation
Proteins
Proteomics
Reactive Oxygen Species
Flow Cytometry
Apoptosis
Cell Cycle Proteins
Annexin A5
Oxidative Phosphorylation
G1 Phase
Electron Transport
Cell Cycle Checkpoints
Ovarian epithelial cancer
tolfenamic acid
S Phase
DNA Damage
Cell Movement
Cell Survival
Cell Cycle

Keywords

  • Cisplatin
  • Epithelial ovarian cancer
  • Sp1
  • Survivin
  • Tolfenamic acid

Cite this

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title = "Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation",
abstract = "The expression of specificity protein 1 (Sp1) and survivin was evaluated in clinical specimens of epithelial ovarian cancer (EOC) patients. When compared to normal tissue, EOC samples showed high expression of Sp1 and survivin using qPCR (Sp1: ∼2-fold; survivin: ∼5-fold) and Western blot (Sp1: >2.6-fold; survivin: >100-fold). The Sp1 inhibitor, and anti-cancer small molecule, tolfenamic acid (TA), was tested to enhance the response of Cisplatin (Cis) in EOC cell lines. Cell viability (CellTiter-Glo), combination index (CalcuSyn software), apoptosis (Annexin-V staining), cell cycle analyses (flow cytometry), and reactive oxygen species (flow cytometry) were determined. Cell migration and invasion was assessed using matrigel coated transwell chambers. Agilent Technologies proteomics analysis identified potential signaling pathways involved. The combination of TA (50 μM) and Cis (5 μM) synergistically increased the growth inhibition in ES2 (∼80 {\%}, p < 0.001) and OVCAR-3 (60 {\%}, p < 0.001) cells. TA or TA + Cis treatment in ES2 cells caused cell cycle arrest in G1 Phase (TA) or S-Phase (TA + Cis) and unregulated reactive oxygen species. Invasion and migration was decreased in ES2 cells. Global proteomic profiling showed modulation of proteins associated with oxidative phosphorylation, apoptosis, electron transport chain, DNA damage, and cell cycle proteins. These results demonstrate an association of Sp1 and survivin in EOC and confirm targeting these candidates with TA potentially sensitizes EOC cells to cisplatin.",
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Association of Sp1 and survivin in epithelial ovarian cancer : Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation. / Sankpal, Umesh Tanaji; Ingersoll, Susan B.; Ahmad, Sarfraz; Holloway, Robert W.; Bhat, Vadiraja B.; Simecka, Jerry; Daniel, Liz; Kariali, Ekamber; Vishwanatha, Jamboor K.; Basha, Riyaz Mahammad.

In: Tumor Biology, Vol. 37, No. 10, 01.10.2016, p. 14259-14269.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation

AU - Sankpal, Umesh Tanaji

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AU - Holloway, Robert W.

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AU - Vishwanatha, Jamboor K.

AU - Basha, Riyaz Mahammad

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