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Updated: Sep 11, 2025
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Targeting Cellular Senescence with Liposome-Encapsulated Fisetin: Evidence of Senomorphic Effect
Agata Henschke1, Bartosz Grześkowiak1, Olena Ivashchenko1
1NanoBioMedical Centre, Adam Mickiewicz University, Wszechnicy Piastowskiej 3, 61-614 Poznan, Poland.
Abstract:
Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin's hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin's therapeutic efficacy, showing comparable results even at the lowest tested concentration.
Insights
Liposomal fisetin effectively reduced harmful secretions from senescent cells, demonstrating senomorphic activity without inducing cell death. This liposomal drug delivery enhances fisetin
Area of Science:
- Cell Biology
- Pharmacology
- Oncology
Background:
- Cellular senescence is implicated in cancer progression, recurrence, and metastasis.
- Senotherapy targets senescent cells via senolytic (apoptosis induction) or senomorphic (SASP suppression) approaches.
- Fisetin is a senotherapeutic agent with potential therapeutic applications.
Purpose of the Study:
- To evaluate the efficacy of liposome-encapsulated fisetin as a senotherapeutic.
- To investigate the senolytic and senomorphic effects of liposomal fisetin on doxorubicin-induced senescent cells.
- To assess the impact of liposomal delivery on fisetin's cellular uptake and therapeutic potential.
Main Methods:
- Senescence was induced in WI-38 (normal lung fibroblasts) and A549 (lung carcinoma) cell lines using doxorubicin.
- Liposomal fisetin was prepared to enhance the delivery of hydrophobic fisetin.
- Senescence markers including SA-β-gal activity, proliferation, morphology, and IL-6/IL-8 secretion were analyzed.
- Cellular uptake of liposomes was confirmed using uptake studies.
Main Results:
- Liposomal fisetin exhibited no senolytic activity, meaning it did not induce apoptosis in senescent cells.
- A significant reduction in pro-inflammatory cytokines IL-6 and IL-8 secretion was observed, indicating senomorphic effects.
- Liposomal encapsulation facilitated effective cellular uptake of fisetin in both normal and cancer-derived senescent cells.
- Enhanced therapeutic efficacy was noted, with significant results even at the lowest tested concentration.
Conclusions:
- Liposomal fisetin demonstrates potent senomorphic activity by suppressing the senescence-associated secretory phenotype.
- Liposomal delivery enhances fisetin's efficacy and cellular penetration for senotherapy.
- This formulation holds promise for managing senescence-related pathologies, particularly in cancer contexts.
