Doxorubicin induces a reversible senescence-like state in the EPC fish cell line

Area of Science:

• Cell Biology
• Comparative Biology

Background:

• Cellular senescence is a stable, irreversible cell cycle arrest triggered by stress, crucial in mammals.
• Fish cells display inherent resistance to stable senescence, with limited understanding of its modulation.

Purpose of the Study:

• To investigate the effects of doxorubicin (DOX), a DNA-damaging agent, on senescence in the fish cell line Epithelioma papulosum cyprini (EPC).
• To determine if fish cells can undergo stable senescence or if their response is transient and reversible.

Main Methods:

• EPC cells were treated with doxorubicin (DOX).
• Assessed for senescence-associated phenotypes: morphological changes, SA-β-gal activity, and SASP factor secretion.
• Monitored cell proliferation and transcriptional states post-treatment.

Main Results:

• DOX induced senescence-associated phenotypes in EPC cells, including SA-β-gal activity and SASP factor secretion.
• Despite these markers, EPC cells did not achieve irreversible cell cycle arrest and could resume proliferation.
• Senescence responses were dynamic and not stably maintained, indicating reversibility.

Conclusions:

• Doxorubicin-induced DNA damage triggers a transient and reversible senescence-like state in EPC cells, not a stable arrest.
• These findings underscore fundamental distinctions between teleost (fish) and mammalian senescence pathways.