Evidence map›Paper›PMID 25010292›Full record

ArticleCancer biology & therapy2014

A novel bisindole-PBD conjugate causes DNA damage induced apoptosis via inhibition of DNA repair pathway.

Pranjal Sarma, M Janaki Ramaiah, Ahmed Kamal, Utpal Bhadra, Manika Pal Bhadra

Open access · bronzeAbstract read
In one paragraph

Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

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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

5 authors at 2 institutions in 2 countries.

Pranjal Sarma1 Centre for Chemical Biology; CSIR-Indian Institute of Chemical Technology; Tarnaka, Hyderabad, India; Functional Genomics and Gene Silencing Group; Centre for Cellular and Molecular Biology; Hyderabad, India.
M Janaki Ramaiah1 Centre for Chemical Biology; CSIR-Indian Institute of Chemical Technology; Tarnaka, Hyderabad, India.
Ahmed KamalMedicinal Chemistry and Pharmacology; CSIR-Indian Institute of Chemical Technology; Tarnaka, Hyderabad, India.
Utpal BhadraFunctional Genomics and Gene Silencing Group; Centre for Cellular and Molecular Biology; Hyderabad, India.
Manika Pal Bhadra1 Centre for Chemical Biology; CSIR-Indian Institute of Chemical Technology; Tarnaka, Hyderabad, India.
Indian Institute of Chemical Technology · INCentre for Cellular and Molecular Biology · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA damage response (DDR) that includes cell cycle check points, DNA repair, apoptosis, and senescence is intimately linked with cancer. It shields an organism against cancer development when genomic integrity fails. DNA repair pathways protect the cells from tumor progression caused as a result of DNA damage induced by irradiation or due to chemotherapeutic treatment. Many promising anticancer agents have been identified that target specific DNA repair pathways in response to DNA damage thereby leading to apoptosis. Here we identified a novel bisindole-PBD conjugate that possess potent anticancer activity in breast cancer cells. Further studies aimed at understanding the mechanism of action of the molecule showed its role in DNA damage induced apoptosis via inhibition of DNA repair pathway. Trypan blue and BrdU assay exhibited a dose-dependent effect. Single-stranded DNA damage was observed by COMET assay. In addition DNA damage induced ROS generation with simultaneous activation of ATM and ATR upon compound treatment was observed. Further downregulation of Bcl-XL and activation of Bax showed DNA damage induced apoptosis in MCF-7 and MDAMB-231 cells. In conclusion, it can be summarized that bisindole-PBD conjugate induces DNA damage in a dose dependent (2, 4, and 8 μM) manner by inhibiting the DNA repair genes.

Indexed as

Antineoplastic AgentsApoptosisbcl-2-Associated X Proteinbcl-X ProteinBenzodiazepinesCell Line, TumorDNA DamageDNA RepairHumansIndolesMitochondrial MembranesPyrrolesReactive Oxygen SpeciesAntineoplastic AgentsBAX protein, humanbcl-2-Associated X Proteinbcl-X ProteinBenzodiazepinesIndolesPyrrolespyrrolo(2,1-c)(1,4)benzodiazepineReactive Oxygen SpeciesapoptosisATRDNA damageDNA repairROS

Identifiers

PMID25010292
PMCPMC4130725
OpenAlexW1997413134

What OpenQuestion holds

Textmetadata
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.