Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence

Abdelgawad, Ibrahim Y.; Sadak, Karim Thomas; Lone, Diana W; Dabour, Mohamed S.; Niedernhofer, Laura J.; Zordoky, Beshay N.

doi:10.1016/j.pharmthera.2020.107751

Cited by 33 publications

(22 citation statements)

References 292 publications

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“…Our in vitro senescence model could be useful as a platform to further evaluate the effectiveness of novel molecules such as senolytics, protein synthesis inhibitors, inhibitors of specific amino acid transporters, glycolytic inhibitors and nutraceuticals on senescence processes by SASP and transcriptome analysis. Future metabolism studies coupled with other investigations regarding the role of senescence in chemo-radiation [ 65 ] may provide a better understanding of how senescence influences tumor response following IR treatment in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells

Nagineni

Naz

Choudhuri

et al. 2021

IJMS

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Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-β1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells

Nagineni

Naz

Choudhuri

et al. 2021

IJMS

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“…Modeling the impact of GCR exposure on the cardiovascular system has proven exceedingly difficult ( Davis et al., 2021 ). Clinical and epidemiologic data obtained from studies of survivors of nuclear accidents, atomic bomb exposure, and radiation-based medical treatments have demonstrated that acute radiation exposure is associated with a higher rate of delayed cardiovascular-related morbidity and mortality ( Ledsome, 2001 ; Taddeo and Armstrong, 2008 ; Baker et al., 2011 ; Adams et al., 2017 ; ; Abdelgawad et al., 2021 ). These studies are limited by confounding factors such as cancer comorbidity, follow-up time post radiation exposure, and estimations of radiation dose.…”

Section: Introductionmentioning

confidence: 99%

Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure

et al. 2022

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“…Inhibits Bcl-2 in tumour and senescent cells. [49,[80][81][82][83] Dasatinib + Quercetin Increased killing of p16 + and p21 + senescent cells.…”

Section: The New Frontier Of Senolytics In Doxo Cardiotoxicitymentioning

confidence: 99%

The Interplay Between Autophagy and Senescence in Anthracycline Cardiotoxicity

Russo

Bono

Ghigo

2021

Curr Heart Fail Rep

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Purpose of Review Doxorubicin (DOXO) is a highly effective chemotherapeutic drug employed for the treatment of a wide spectrum of cancers, spanning from solid tumours to haematopoietic malignancies. However, its clinical use is hampered by severe and dose-dependent cardiac side effects that ultimately lead to heart failure (HF). Recent Findings Mitochondrial dysfunction and oxidative stress are well-established mechanisms of DOXO-induced cardiotoxicity, although recent evidence suggests that deregulation of other biological processes, like autophagy, could be involved. It is increasingly recognized that autophagy deregulation is intimately interconnected with the initiation of detrimental cellular responses, including autosis and senescence, raising the possibility of using autophagy modulators as well as senolytics and senomorphics for preventing DOXO cardiotoxicity. Summary This review aims at providing an overview of the signalling pathways that are common to autophagy and senescence, with a special focus on how the relationship between these two processes is deregulated in response to cardiotoxic treatments. Finally, we will discuss the potential therapeutic utility of drugs modulating autophagy and/or senescence for counteracting DOXO cardiotoxicity.

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Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence

Cited by 33 publications

References 292 publications

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells

Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure

The Interplay Between Autophagy and Senescence in Anthracycline Cardiotoxicity

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