Evidence map›Paper›PMID 24710119›Full record

ArticlePloS one2014

Lactaptin induces p53-independent cell death associated with features of apoptosis and autophagy and delays growth of breast cancer cells in mouse xenografts.

Olga A Koval, Anastasiya V Tkachenko, Alexandr S Fomin, Dmitry V Semenov, Anna A Nushtaeva, Elena V Kuligina, Eugeny L Zavjalov, Vladimir A Richter

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 34 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

8 authors at 2 institutions in 1 country.

Olga A KovalInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.
Anastasiya V TkachenkoInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia.
Alexandr S FominInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia.
Dmitry V SemenovInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia.
Anna A NushtaevaInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia.
Elena V KuliginaInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia.
Eugeny L ZavjalovInstitute of Cytology and Genetics SB RUS, Novosibirsk, Russia.
Vladimir A RichterInstitute of Chemical Biology and Fundamental Medicine SB RUS, Novosibirsk, Russia.
Institute of Chemical Biology and Fundamental Medicine · RUInstitute of Cytology and Genetics · RU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lactaptin, the proteolytic fragment of human milk kappa-casein, induces the death of various cultured cancer cells. The mechanisms leading to cell death after lactaptin treatment have not been well characterized. In this study the in vivo and in vitro effects of a recombinant analogue of lactaptin (RL2) were examined. Following treatment with the recombinant analogue of lactaptin strong caspase -3, -7 activation was detected. As a consequence of caspase activation we observed the appearance of a sub-G1 population of cells with subdiploid DNA content. Dynamic changes in the mRNA and protein levels of apoptosis-related genes were estimated. No statistically reliable differences in p53 mRNA level or protein level were found between control and RL2-treated cells. We observed that RL2 constitutively suppressed bcl-2 mRNA expression and down regulated Bcl-2 protein expression in MDA-MB-231 cells. We demonstrated that RL2 penetrates cancer and non-transformed cells. Identification of the cellular targets of the lactaptin analogue revealed that α/β-tubulin and α-actinin-1 were RL2-bound proteins. As the alteration in cellular viability in response to protein stimulus can be realized not only by way of apoptosis but also by autophagy, we examined the implications of autophagy in RL2-dependent cell death. We also found that RL2 treatment induces LC3-processing, which is a hallmark of autophagy. The autophagy inhibitor chloroquine enhanced RL2 cytotoxicity to MDA-MB-231 cells, indicating the pro-survival effect of RL2-dependent autophagy. The antitumour potential of RL2 was investigated in vivo in mouse xenografts bearing MDA-MB-231 cells. We demonstrated that the recombinant analogue of lactaptin significantly suppressed the growth of solid tumours. Our results indicate that lactaptin could be a new molecule for the development of anticancer drugs.

Indexed as

AnimalsAntineoplastic AgentsApoptosisAutophagyBreast NeoplasmsCaseinsCaspasesCell DeathCell Line, TumorCell SurvivalChloroquineDNA FragmentationHeterograftsHumansMiceProto-Oncogene Proteins c-bcl-2Antineoplastic AgentsCaseinsCaspasesChloroquinelactaptin, humanProto-Oncogene Proteins c-bcl-2

Identifiers

PMID24710119
PMCPMC3978064
OpenAlexW2074350582

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.