Mitochondrial Peptide Humanin Facilitates Chemoresistance in Glioblastoma Cells.

Peña Agudelo JA, Pidre ML, Garcia Fallit M, Pérez Küper M, Zuccato C, Nicola Candia AJ, Marchesini A, Vera MB, De Simone E, Giampaoli C, Amorós Morales LC, Gonzalez N and 4 more

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Romanowski V, Videla-Richardson GA, Seilicovich A, Candolfi M

Cancers11 Aug 2023Cited by 14 (Europe PMC)

PMID37627089PMCIDPMC10452904DOI10.3390/cancers15164061PepBankPUB-37627089

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Summary

Humanin (HN) is a mitochondrial-derived peptide with robust cytoprotective effects in many cell types. Although the administration of HN analogs has been proposed to treat degenerative diseases, its role in the pathogenesis of cancer is poorly understood. Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells. We found that chemotherapy upregulated HN expression in GBM cell lines and primary cultures derived from GBM biopsies. An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation. Chemotherapy also upregulated FPR2 expression, an HN membrane-bound receptor, and the HNGF6A cytoprotective effects were inhibited by an FPR2 receptor antagonist (WRW4). These effects were observed in glioma cells with heterogeneous genetic backgrounds, i.e., glioma cells with wild-type (wtIDH) and mutated (mIDH) isocitrate dehydrogenase. HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells. Taken together, our findings suggest that HN boosts the hallmark characteristics of GBM, i.e., chemoresistance, migration and endothelial cell proliferation. Thus, strategies that inhibit the HN/FPR2 pathway may improve the response of GBM to standard therapy.

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

Results from this study7

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

Natural levels measured1

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
In glioblastoma cell lines and primary GBM cultures, chemotherapy increased expression of the cells' own humanin.
In plain wordsIn glioblastoma cells, chemotherapy raised the cells' own humanin levels.
Peptide
Humanin
Outcome
IncreaseHN expression after chemotherapy
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
We found that chemotherapy upregulated HN expression in GBM cell lines and primary cultures derived from GBM biopsies.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3762708901

Studies that did not test the peptide alone6

In this study, Humanin 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 Humanin.

02LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In glioblastoma cells, the humanin analog HNGF6A increased chemoresistance.
In plain wordsIn lab tests, a humanin analog made glioblastoma cells more resistant to chemotherapy.
Peptide
Humanin
Outcome
IncreaseChemoresistance with HN analog HNGF6A
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Tumor growth · Cancer
Source sentences
Summary
An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-3762708902
03LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In glioblastoma cells, the humanin analog HNGF6A increased cell migration.
In plain wordsIn lab tests, a humanin analog made glioblastoma cells move more.
Peptide
Humanin
Outcome
IncreaseGBM cell migration with HNGF6A
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Tumor growth · Cancer
Source sentences
Summary
An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-3762708903
04LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In glioblastoma cells, the humanin analog HNGF6A improved the capacity of the cells to induce endothelial cell migration and proliferation.
In plain wordsIn lab tests, a humanin analog made glioblastoma cells better at driving blood vessel cell growth and movement.
Peptide
Humanin
Outcome
IncreaseEndothelial cell migration and proliferation induced by GBM cells with HNGF6A
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Tumor growth · Cancer
Source sentences
Summary
An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-3762708904
05LabNot a test of Humanin aloneIn vitro (cells)Mechanism
In glioblastoma cells, the FPR2 antagonist WRW4 inhibited the cytoprotective effects of the humanin analog HNGF6A.
In plain wordsIn lab tests, blocking the FPR2 receptor stopped the protective effect of a humanin analog in glioblastoma cells.
Peptide
Humanin
Outcome
DecreaseHNGF6A cytoprotective effect with FPR2 antagonist WRW4
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
Chemotherapy also upregulated FPR2 expression, an HN membrane-bound receptor, and the HNGF6A cytoprotective effects were inhibited by an FPR2 receptor antagonist (WRW4).
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-3762708905
06LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In glioblastoma cells, silencing of the HN gene with a baculoviral shRNA vector reduced chemoresistance.
In plain wordsIn lab tests, switching off the humanin gene made glioblastoma cells less resistant to chemotherapy.
Peptide
Humanin
Outcome
DecreaseChemoresistance after HN silencing
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Tumor growth · Cancer
Source sentences
Summary
HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-3762708906
07LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In glioblastoma cells, silencing of the HN gene with a baculoviral shRNA vector impaired cell migration and proangiogenic capacity.
In plain wordsIn lab tests, switching off the humanin gene made glioblastoma cells move less and drive less blood vessel growth.
Peptide
Humanin
Outcome
DecreaseMigration and proangiogenic capacity after HN silencing
Study
humann: not reported in source
Glioblastoma cell lines and primary cultures from GBM biopsies
Outcome group
Tumor growth · Cancer
Source sentences
Summary
HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-3762708907

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, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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