Evidence map›Paper›PMID 27188390›Full record

ArticleTargeted oncology2016

Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines.

Mahesh Hegde, Kempegowda Mantelingu, Monica Pandey, Chottanahalli S Pavankumar, Kanchugarakoppal S Rangappa, Sathees C Raghavan

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Article in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

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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

5 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Mahesh HegdeDepartment of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.
Kempegowda MantelinguDepartment of Studies in Chemistry, Manasagangotri, University of Mysore, Mysuru, 570006, India.
Monica PandeyDepartment of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.
Chottanahalli S PavankumarDepartment of Studies in Chemistry, Manasagangotri, University of Mysore, Mysuru, 570006, India.
Kanchugarakoppal S RangappaDepartment of Studies in Chemistry, Manasagangotri, University of Mysore, Mysuru, 570006, India. rangappaks@chemistry.uni-mysore.ac.in.
Sathees C RaghavanDepartment of Biochemistry, Indian Institute of Science, Bangalore, 560012, India. sathees@biochem.iisc.ernet.in.
University of Mysore · INIndian Institute of Science Bangalore · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics.

objectiveThe purpose of this study was to investigate the combinatorial effects of a novel PARP inhibitor, P10, and HDAC inhibitor, SAHA, in leukemic cells.

methodsCombinatorial effects of P10 and SAHA were tested using propidium iodide staining in different leukemic cells. Further, flowcytometry-based assays such as calcein-AM/ethidium homodimer staining, annexin-FITC/PI staining, and JC-1 staining were carried out to elucidate the mechanism of cell death. In addition, cell-cycle analysis, immunocytochemistry studies, and western blotting analysis were conducted to check the combinatorial effect in Nalm6 cells.

resultsPropidium iodide staining showed that P10 in combination with SAHA induced cell death in Nalm6 cells, in which PARP expression and activity is high with a combination index of <0.2. Annexin-FITC/PI staining, JC-1 staining, and other biochemical assays revealed that P10 in combination with SAHA induced apoptosis by causing a change in mitochondrial membrane potential in >65 % cells. Importantly, combinatorial treatment induced S phase arrest in 40-45 % cells due to DNA damage and plausible replicative stress. Finally, we demonstrated that treatment with P10 led to DNA strand breaks, which were further potentiated by SAHA (p < 0.01), leading to activation of apoptosis and increased cell death in PARP-positive leukemic cells.

conclusionsOur study reveals that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity.

Indexed as

Cell Line, TumorCell ProliferationHistone Deacetylase InhibitorsHumansLeukemiaPoly(ADP-ribose) Polymerase InhibitorsHistone Deacetylase InhibitorsPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID27188390
OpenAlexW2400872569

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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.