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Study · In vitro (cells) · rat · 2026

7 results

Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence.

Fan J, Wu J, Yan S, Li S, Rabinovitch PS, Qi X, Zhang H

Biology28 Jun 2026

PMID42450582 (opens in a new tab)PMCIDPMC13359912 (opens in a new tab)DOI10.3390/biology15131034 (opens in a new tab)PepBankPUB-42450582
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Summary

Doxorubicin (DOX), an effective chemotherapeutic agent for many types of cancer, is known for significant cardiotoxic side effects, which largely limit its clinical usage. A 3 h treatment of cardiomyoblast H9C2 cells with a low concentration of DOX (100 nM) can induce senescence-associated β-galactosidase (SA β-gal) staining, a gold standard of cell senescence. In the current study, we comprehensively characterized the phenotype of the DOX-induced senescent cardiomyocytes for the first time. Establishing this in vitro model will facilitate an expanded capacity for searching for effective treatments for DOX-induced cell senescence. Using SA β-gal staining and cell growth rate as readouts, we assessed the concentration-dependent effect of DOX on H9C2 cell senescence. The cells were treated with DOX for 3 h and subsequently cultured for 3 days. We found that a 50 nM concentration of DOX induced ~50% SA β-gal staining and completely inhibited cell growth. The DOX-induced H9C2 cell senescence was further confirmed by several well-accepted senescence markers, including cell hypertrophy, increased p16 and p21 expression, increased Senescence Associated Secretory Phenotype (SASP) markers, arrested cell cycle, and increased ROS production. Interestingly, we found that 50 nM DOX increased mitochondrial respiration. Translationally, we found that mitochondrial-targeted tetrapeptide SS-31 (elamipretide, 1 µM) partially attenuated 50 nM DOX-induced SA β-gal staining from 51.4% to 35.8%. SS-31 also prevented increases in the p16, p21, and SASP markers and mitigated mitochondrial ROS production. Additionally, SS-31 reversed the 50 nM DOX-induced elevation of mitochondrial respiration. However, 1 µM SS-31 failed to prevent the cell cycle arrest induced by 50 nM DOX. Using a 3 h treatment of 50 nM DOX, we established an H9C2 cell senescence model. Treatment with SS-31 attenuates this DOX-induced cell senescence but not the cell cycle arrest. These data suggest that SS-31 is a promising drug to treat DOX-induced cardiomyocyte senescence.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In H9C2 cells with doxorubicin-induced senescence, SS‑31 at 1 µM partially attenuated SA β-gal staining from 51.4% to 35.8%.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 partly reduced a common sign of cell ageing compared with untreated cells.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseSA beta-gal staining
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Aging markers · Cardiovascular
    Studied dose
    1 µMAs given in this study (rat).

    Measurements

    SA β-gal staining
    35.8%
    SS-31 1 µM + 50 nM DOX
    SA β-gal staining
    51.4%
    50 nM DOX alone

    Source sentences

    Summary
    Translationally, we found that mitochondrial-targeted tetrapeptide SS-31 (elamipretide, 1 µM) partially attenuated 50 nM DOX-induced SA β-gal staining from 51.4% to 35.8%.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.
  2. 02LabIn vitro (cells)Mechanism

    In H9C2 cells with doxorubicin-induced senescence, SS‑31 prevented the increase in p16.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 stopped a rise in p16, a marker of cell ageing.

    Peptide
    Elamipretide (SS-31)
    Outcome
    Decreasep16 expression
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Aging markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SS-31 also prevented increases in the p16, p21, and SASP markers and mitigated mitochondrial ROS production.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.
  3. 03LabIn vitro (cells)Mechanism

    In H9C2 cells with doxorubicin-induced senescence, SS‑31 prevented the increase in p21.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 stopped a rise in p21, a marker of cell ageing.

    Peptide
    Elamipretide (SS-31)
    Outcome
    Decreasep21 expression
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Aging markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SS-31 also prevented increases in the p16, p21, and SASP markers and mitigated mitochondrial ROS production.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.
  4. 04LabIn vitro (cells)Mechanism

    In H9C2 cells with doxorubicin-induced senescence, SS‑31 prevented the increase in senescence-associated secretory phenotype markers.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 stopped a rise in inflammation signals released by ageing cells.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseSASP markers
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SS-31 also prevented increases in the p16, p21, and SASP markers and mitigated mitochondrial ROS production.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.
  5. 05LabIn vitro (cells)Mechanism

    In H9C2 cells with doxorubicin-induced senescence, SS‑31 mitigated mitochondrial ROS production.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 reduced harmful reactive oxygen molecules made by mitochondria.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseMitochondrial ROS production
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SS-31 also prevented increases in the p16, p21, and SASP markers and mitigated mitochondrial ROS production.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.
  6. 06LabIn vitro (cells)Mechanism

    In H9C2 cells, SS‑31 reversed the elevation of mitochondrial respiration induced by 50 nM doxorubicin.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 reversed a rise in mitochondrial oxygen use.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseMitochondrial respiration
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Additionally, SS-31 reversed the 50 nM DOX-induced elevation of mitochondrial respiration.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.
  7. 07LabIn vitro (cells)Mechanism

    In H9C2 cells, SS‑31 at 1 µM failed to prevent the cell cycle arrest induced by 50 nM doxorubicin.

    In plain wordsIn heart cells aged by a cancer drug, SS‑31 did not stop cells from halting their division cycle.

    Peptide
    Elamipretide (SS-31)
    Outcome
    No significant changeCell cycle arrest
    Study

    ratn: not reported in source

    H9C2 cardiomyoblasts with 50 nM doxorubicin-induced senescence
    Comparator
    Doxorubicin-treated cells without SS-31
    Outcome group
    Aging markers · Cardiovascular
    Studied dose
    1 µMAs given in this study (rat).

    Source sentences

    Summary
    However, 1 µM SS-31 failed to prevent the cell cycle arrest induced by 50 nM DOX.
    1 context sentence
    Summary · context
    The cells were treated with DOX for 3 h and subsequently cultured for 3 days.

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.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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