Evidence map›Paper›PMID 28086831›Full record

ArticleBMC cancer2017

Evaluation of the cytotoxicity of the Bithionol - cisplatin combination in a panel of human ovarian cancer cell lines.

Vijayalakshmi N Ayyagari, Tsung-Han Jeff Hsieh, Paula L Diaz-Sylvester, Laurent Brard

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Mapping the Landscape of Global Anticancer Organometallics Research: A Systematic Review.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Balkan journal of medical genetics : BJMG · 2019
    Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Vijayalakshmi N AyyagariDivision of Gynecologic Oncology; Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Tsung-Han Jeff HsiehDivision of Gynecologic Oncology; Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Paula L Diaz-SylvesterDivision of Gynecologic Oncology; Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Laurent BrardDivision of Gynecologic Oncology; Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, IL, USA. lbrard@siumed.edu.
Southern Illinois University School of Medicine · USCenter for Clinical Research (United States) · USGynecologic Oncology Group · US

Funding

Training and Education CoreP20CA192987 · NCI · SOUTHERN ILLINOIS UNIVERSITY SCH OF MED · PI BRARD, LAURENT · 2015 to 2017
$653k
NCI NIH HHS P20 CA192987
6 · The paper itself

Abstract

backgroundCombination drug therapy appears a promising approach to overcome drug resistance and reduce drug-related toxicities in ovarian cancer treatments. In this in vitro study, we evaluated the antitumor efficacy of cisplatin in combination with Bithionol (BT) against a panel of ovarian cancer cell lines with special focus on cisplatin-sensitive and cisplatin-resistant cell lines. The primary objectives of this study are to determine the nature of the interactions between BT and cisplatin and to understand the mechanism(s) of action of BT-cisplatin combination.

methodsThe cytotoxic effects of drugs either alone or in combination were evaluated using presto-blue assay. Cellular reactive oxygen species were measured by flow cytometry. Immunoblot analysis was carried out to investigate changes in levels of cleaved PARP, XIAP, bcl-2, bcl-xL, p21 and p27. Luminescent and colorimetric assays were used to test caspases 3/7 and ATX activity.

resultsThe efficacy of the BT-cisplatin combination depends upon the cell type and concentrations of cisplatin and BT. In cisplatin-sensitive cell lines, BT and cisplatin were mostly antagonistic except when used at low concentrations, where synergy was observed. In contrast, in cisplatin-resistant cells, BT-cisplatin combination treatment displayed synergistic effects at most of the drug ratios/concentrations. Our results further revealed that the synergistic interaction was linked to increased reactive oxygen species generation and apoptosis. Enhanced apoptosis was correlated with loss of pro-survival factors (XIAP, bcl-2, bcl-xL), expression of pro-apoptotic markers (caspases 3/7, PARP cleavage) and enhanced cell cycle regulators p21 and p27.

conclusionIn cisplatin-resistant cell lines, BT potentiated cisplatin-induced cytotoxicity at most drug ratios via enhanced ROS generation and modulation of key regulators of apoptosis. Low doses of BT and cisplatin enhanced efficiency of cisplatin treatment in all the ovarian cancer cell lines tested. Our results suggest that novel combinations such as BT and cisplatin might be an attractive therapeutic approach to enhance ovarian cancer chemosensitivity. Combining low doses of cisplatin with subtherapeutic doses of BT can ultimately lead to the development of an innovative combination therapy to reduce/prevent the side effects normally occurring when high doses of cisplatin are administered.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsApoptosisBiomarkers, TumorBithionolCell Line, TumorCisplatinDrug Resistance, NeoplasmFemaleHumansOvarian NeoplasmsReactive Oxygen SpeciesBiomarkers, TumorBithionolCisplatinReactive Oxygen SpeciesApoptosisAutotaxinBithionolCisplatinDrug combinationOvarian cancer cell linesReactive oxygen species

Identifiers

PMID28086831
PMCPMC5234112
OpenAlexW2578968110

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.