Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Mabrouk, Nesrine; Ghione, S; Laurens, Véronique; Plenchette, Stéphanie; Bettaı̈eb, Ali; Paul, Catherine

doi:10.3390/cancers12051145

Cited by 16 publications

(16 citation statements)

References 148 publications

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“…Moreover, NO has also been demonstrated to induce apoptosis in OA synoviocytes and chondrocytes by activating the expression of pro-apoptotic caspase-3 and caspase-9 [ 59 ]. In the context of cellular senescence, NO is thought to act as a modulator of various SASP pathways and as an inducer of SIPS due to direct or indirect DNA damage, mediated by its highly reactive derivatives such as peroxynitrites [ 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes

Kirsch

Ramge

Schoppa

et al. 2022

Cells

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Accumulation of senescent chondrocytes is thought to drive inflammatory processes and subsequent cartilage degeneration in age-related as well as posttraumatic osteoarthritis (OA). However, the underlying mechanisms of senescence and consequences on cartilage homeostasis are not completely understood so far. Therefore, suitable in vitro models are needed to study chondrocyte senescence. In this study, we established and evaluated a doxorubicin (Doxo)-based model of stress-induced premature senescence (SIPS) in human articular chondrocytes (hAC). Cellular senescence was determined by the investigation of various senescence associated (SA) hallmarks including β-galactosidase activity, expression of p16, p21, and SA secretory phenotype (SASP) markers (IL-6, IL-8, MMP-13), the presence of urokinase-type plasminogen activator receptor (uPAR), and cell cycle arrest. After seven days, Doxo-treated hAC displayed a SIPS-like phenotype, characterized by excessive secretion of SASP factors, enhanced uPAR-positivity, decreased proliferation rate, and increased β-galactosidase activity. This phenotype was proven to be stable seven days after the removal of Doxo. Moreover, Doxo-treated hAC exhibited increased granularity and flattened or fibroblast-like morphology. Further analysis implies that Doxo-mediated SIPS was driven by oxidative stress as demonstrated by increased ROS levels and NO release. Overall, we provide novel insights into chondrocyte senescence and present a suitable in vitro model for further studies.

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Section: Discussionmentioning

confidence: 99%

In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes

Kirsch

Ramge

Schoppa

et al. 2022

Cells

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“…Molecular specification of senescence depends on the type of stimulus as well as the environmental conditions of the cell [ 162 ]. Senescent cells are secretory active, making SASP a common but highly heterogeneous senescence-associated feature [ 66 , 68 , 69 ]. The majority of secreted molecules are associated with inflammation and have the potential to both benefit and harm the cell and its environment [ 69 , 135 ].…”

Section: Discussionmentioning

confidence: 99%

“…Pathways responsible for the induction of the senescence-associated secretory phenotype (SASP). Schematic representation of major pathways that are activated in senescent cells leading to the expression of SASP genes (left panel).Most important SASP factors according to[68][69][70] (right panel). cDN, cyclic dinucleotides.…”

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confidence: 99%

Molecular Mechanisms of Senescence and Implications for the Treatment of Myeloid Malignancies

Ernst

Heidel

2021

Cancers

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Senescence is a cellular state that is involved in aging-associated diseases but may also prohibit the development of pre-cancerous lesions and tumor growth. Senescent cells are actively secreting chemo- and cytokines, and this senescence-associated secretory phenotype (SASP) can contribute to both early anti-tumorigenic and long-term pro-tumorigenic effects. Recently, complex mechanisms of cellular senescence and their influence on cellular processes have been defined in more detail and, therefore, facilitate translational development of targeted therapies. In this review, we aim to discuss major molecular pathways involved in cellular senescence and potential therapeutic strategies, with a specific focus on myeloid malignancies.

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“…[ 28 ] Hence, strategies interfering with the antiapoptotic pathway might enable the selective clearance of senescent cells. [ 29 , 30 , 31 ] Highly selective targeted drug delivery systems might target the impaired tissue, achieve better therapeutic efficiency and reduce side effects. [ 32 , 33 ] Consequently, the design of a selective targeted drug delivery system loaded with an effective therapeutic factor for chronic wound healing is still a challenge for researchers.…”

Section: Introductionmentioning

confidence: 99%

Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation

Zhao

Jin

et al. 2021

Advanced Science

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Diabetic ulcers, a difficult problem faced by clinicians, are strongly associated with an increase in cellular senescence. Few empirical studies have focused on exploring a targeted strategy to cure diabetic wounds by eliminating senescent fibroblasts (SFs) and reducing side effects. In this study, poly-l-lysine/sodium alginate (PLS) is modified with talabostat (PT100) and encapsulates a PARP1 plasmid (PARP1@PLS-PT100) for delivery to target the dipeptidyl peptidase 4 (DPP4) receptor and eliminate SFs. PARP1@PLS-PT100 releases encapsulated plasmids, displaying high selectivity for SFs over normal fibroblasts by targeting the DPP4 receptor, decreasing senescence-associated secretory phenotypes (SASPs), and stimulating the secretion of anti-inflammatory factors. Furthermore, the increased apoptosis of SFs and the disappearance of cellular senescence alleviates SASPs, accelerates re-epithelialization and collagen deposition, and significantly induces macrophage M2 polarization, which mediates tissue repair and the inflammatory response.

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Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Cited by 16 publications

References 148 publications

In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes

In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes

Molecular Mechanisms of Senescence and Implications for the Treatment of Myeloid Malignancies

Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation

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