Doxorubicin and liposomal doxorubicin induce senescence by enhancing nuclear factor kappa B and mitochondrial membrane potential

Fallah, Marjan; Mohammadi, Hamidreza; Shaki, Fatemeh; Hosseini‐Khah, Zahra; Moloudizargari, Milad; Dashti, Ayat; Ziar, Ali; Mohammadpour, Abbas; Mirshafa, Atefeh; Modanloo, Mona; Shokrzadeh, Mohammad

doi:10.1016/j.lfs.2019.116677

Cited by 17 publications

(12 citation statements)

References 56 publications

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“…The ability of DOX to induce senescence may promote inflammation and exacerbate heart dysfunction (Mitry and Edwards, 2016). Indeed, previous studies demonstrated that DOX induced cardiomyopathy and inflammation (Fallah et al, 2019). Consistent with this, we also showed that DOX at several folds below its LC 50 was sufficient to reduce heart function in zebrafish, as observed in previous findings (Han et al, 2015).…”

Section: Discussionsupporting

confidence: 90%

“…DOX causes topoisomerase-II inhibition, impaired DNA replication, and DNA double strand breaks (Mitry and Edwards, 2016), which can all lead to cellular senescence (Marino Gammazza et al, 2017;Fallah et al, 2019). Indeed, chronic treatment of DOX at low doses can permanently arrest proliferation in MCF-7 cancer cell lines and other cells isolated from different types of solid tumors (Chang et al, 1999;Srdic-Rajic et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Alangium longiflorum Merr. Leaf Extract Induces Apoptosis in A549 Lung Cancer Cells with Minimal NFκB Transcriptional Activation

Marquez

Garcia

Antonio

et al. 2020

Asian Pac J Cancer Prev

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Alangium longiflorum Merr. Leaf Extract Induces Apoptosis in A549 Lung Cancer Cells with Minimal NFκB Transcriptional Activation

Marquez

Garcia

Antonio

et al. 2020

Asian Pac J Cancer Prev

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“…Senescent cells are characterized by biochemical and morphological changes such as flattening and/or nuclear enlargement (508). There are several classical biomarkers of cellular senescence and they comprise: senescence-associated beta-galactosidase (SA-ß-gal) activity, expression of p53 protein, the amount of p53 in the nucleus, increase in expression of p14 (Arf), p16 (Ink4a) and p21 (Waf1), SASP, and often senescenceassociated heterochromatic foci (SAHF) (12,505,507,(509)(510)(511)(512)(513)(514)(515). Furthermore, senescent cells display low Ki67 levels and show levels of heterochromatin protein 1 (HP1) gamma ( 516), as well as di-or tri-methylated lysine 9 of histone H3 (H3K9Me2/3) and histone H2A variant (macroH2A) (505,517,518).…”

Section: Therapy-induced Senescence: Its Hallmarks Biomarkers and Its Role In Csc Generationmentioning

confidence: 99%

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

et al. 2020

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The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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“…Mitochondrial membrane potential (MMP) is formed by the asymmetric distribution of protons and other ions on both sides of the intima during respiratory oxidation and is important for maintaining the normal physiological function of cells [22,23]. LPS disrupts the stability of MMP, which is not conducive to maintaining normal physiological functions of cells [22][23][24]. The fluorescence of MMP and the fluorescence statistic data were shown in Figure 5A,B, respectively, LPS-induced increase of green fluorescence JC-1 was almost completely reversed to red fluorescence by DB, suggesting that DB restored LPS-induced MMP loss.…”

Section: Db Suppresses the Loss Of Mmp And Lps-induced Ros Generationmentioning

confidence: 99%

Diethyl Blechnic Exhibits Anti-Inflammatory and Antioxidative Activity via the TLR4/MyD88 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

Han

et al. 2019

Molecules

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Inflammation is a common pathogenesis in many diseases. Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has been considered to have good anti-inflammatory effects. In the present study, we investigated the anti-inflammatory effect of diethyl blechnic (DB), a novel compound isolated from Danshen, and its possible mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The results showed that DB can inhibit the LPS-induced pro-inflammatory cytokines release of prostaglandin E2 (PGE2) and mRNA expression of TNF-α, IL-6, and IL-1β. In addition, the results of the flow cytometry assay and the fluorometric intracellular ROS kit assay indicated that DB reduced the generation of ROS in LPS-stimualted RAW264.7 cells. DB reversed the LPS-induced loss of the mitochondrial membrane potential (MMP). Furthermore, DB suppressed the LPS-stimulated increased expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and phosphorylation of TAK1, PI3K, and AKT. DB promoted NF-E2-related factor 2 (Nrf2) into the nucleus, increased the expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) and reduced the expression of Keap1. In summary, DB may inhibit LPS-induced inflammation, which mainly occurs through TLR4/MyD88 and oxidative stress signaling pathways in RAW264.7 cells.

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Doxorubicin and liposomal doxorubicin induce senescence by enhancing nuclear factor kappa B and mitochondrial membrane potential

Cited by 17 publications

References 56 publications

Alangium longiflorum Merr. Leaf Extract Induces Apoptosis in A549 Lung Cancer Cells with Minimal NFκB Transcriptional Activation

Alangium longiflorum Merr. Leaf Extract Induces Apoptosis in A549 Lung Cancer Cells with Minimal NFκB Transcriptional Activation

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Diethyl Blechnic Exhibits Anti-Inflammatory and Antioxidative Activity via the TLR4/MyD88 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

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