Di-(2-ethylhexyl) phthalate-induced tumor growth is regulated by primary cilium formation via the axis of H₂O₂ production-thymosin beta-4 gene expression.

Lee JW, Thuy PX, Han HK, Moon EY

International journal of medical sciences14 Jan 2021Cited by 8 (Europe PMC)

PMID33526986PMCIDPMC7847613DOI10.7150/ijms.53595PepBankPUB-33526986

Summary

Di-(2-ethylhexyl) phthalate (DEHP) that is one of the most commonly used phthalates in manufacturing plastic wares regulates tumorigenesis. Thymosin beta-4 (TB4), an actin-sequestering protein, has been reported as a novel regulator to form primary cilia that are antenna-like organelles playing a role in various physiological homeostasis and pathological development including tumorigenesis. Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS). Tumor growth was increased by DEHP treatment that enhanced TB4 expression, PC formation and ROS production. The number of cells with primary cilia was enhanced time-dependently higher in HeLa cells incubated in the culture medium with 0.1% fetal bovine serum (FBS). The number of cells with primary cilia was decreased by the inhibition of TB4 expression. The incubation of cells with 0.1% FBS enhanced ROS production and the transcriptional activity of TB4 that was reduced by ciliobrevin A (CilioA), the inhibitor of ciliogenesis. ROS production was decreased by catalase treatment but not by mito-TEMPO, which affected to PC formation with the same trend. H₂O₂ production was reduced by siRNA-based inhibition of TB4 expression. H₂O₂ also increased the number of ciliated cells, which was reduced by siRNA-TB4 or the co-incubation with CilioA. Tumor cell viability was maintained by ciliogenesis, which was correlated with the changes of intracellular ATP amount rather than a simple mitochondrial enzyme activity. TB4 overexpression enhanced PC formation and DEHP-induced tumor growth. Taken together, data demonstrate that DEHP-induced tumor growth might be controlled by PC formation via TB4-H₂O₂ axis. Therefore, it suggests that TB4 could be a novel bio-marker to expect the risk of DEHP on tumor growth.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

No result from this study comes from a test of the peptide.

Natural levels measured3

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01LabEndogenous levelIn vitro (cells)Mechanism
DEHP treatment increased TB4 expression, together with tumor growth, primary cilium formation and ROS production.
In plain wordsIn the study model, DEHP raised the body's own TB4 levels, along with tumor growth.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseTB4 expression after DEHP treatment
Study
n: not reported in source
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Tumor growth was increased by DEHP treatment that enhanced TB4 expression, PC formation and ROS production.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3352698601
02LabEndogenous levelIn vitro (cells)Mechanism
In HeLa cells, incubation with 0.1% FBS enhanced the transcriptional activity of TB4.
In plain wordsIn cells, low serum raised the activity of the body's own TB4 gene.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseTB4 transcriptional activity with 0.1% FBS
Study
humann: not reported in source
HeLa cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
The incubation of cells with 0.1% FBS enhanced ROS production and the transcriptional activity of TB4 that was reduced by ciliobrevin A (CilioA), the inhibitor of ciliogenesis.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3352698603
03LabEndogenous levelIn vitro (cells)Mechanism
In HeLa cells, ciliobrevin A, an inhibitor of ciliogenesis, reduced the FBS-enhanced transcriptional activity of TB4.
In plain wordsIn cells, a cilia blocker lowered the activity of the body's own TB4 gene.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTB4 transcriptional activity with ciliobrevin A
Study
humann: not reported in source
HeLa cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
The incubation of cells with 0.1% FBS enhanced ROS production and the transcriptional activity of TB4 that was reduced by ciliobrevin A (CilioA), the inhibitor of ciliogenesis.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3352698604

Studies that did not test the peptide alone5

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

04LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In HeLa cells, inhibition of TB4 expression decreased the number of cells with primary cilia.
In plain wordsIn cells, blocking TB4 expression reduced the number of cells with primary cilia.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseCells with primary cilia after TB4 inhibition
Study
humann: not reported in source
HeLa cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
The number of cells with primary cilia was decreased by the inhibition of TB4 expression.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3352698602
05LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In HeLa cells, siRNA inhibition of TB4 expression reduced H2O2 production.
In plain wordsIn cells, silencing the TB4 gene lowered H2O2 production.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseH2O2 production after TB4 siRNA
Study
humann: not reported in source
HeLa cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
H₂O₂ production was reduced by siRNA-based inhibition of TB4 expression.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3352698605
06LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In HeLa cells, siRNA-TB4 or co-incubation with CilioA reduced the increase in ciliated cells caused by H2O2.
In plain wordsIn cells, silencing TB4 or a cilia blocker reduced the rise in ciliated cells caused by H2O2.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseH2O2-induced ciliated cells after TB4 siRNA or CilioA
Study
humann: not reported in source
HeLa cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
H₂O₂ also increased the number of ciliated cells, which was reduced by siRNA-TB4 or the co-incubation with CilioA.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3352698606
07LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In cells, TB4 overexpression enhanced primary cilium formation.
In plain wordsIn cells, extra TB4 gene activity increased the formation of primary cilia.
Peptide
Thymosin beta-4 (human)
Outcome
IncreasePrimary cilium formation after TB4 overexpression
Study
humann: not reported in source
HeLa cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
TB4 overexpression enhanced PC formation and DEHP-induced tumor growth.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3352698607
08LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Efficacy outcome
In cells, TB4 overexpression enhanced DEHP-induced tumor growth.
In plain wordsIn cells, extra TB4 gene activity increased tumor growth that DEHP caused.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseDEHP-induced tumor growth after TB4 overexpression
Study
humann: not reported in source
HeLa cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
TB4 overexpression enhanced PC formation and DEHP-induced tumor growth.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3352698608

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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