Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways

García-Pérez, Ana Isabel; Galeano, Eva; Nieto, Elena; Estañ, María Cristina; Sancho, Pilar

doi:10.1016/j.leukres.2014.01.009

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Previous studies have demonstrated that the ERK and/or AKT pathways may contribute to the cell protective effects of several growth factors via apoptotic inhibition (27,28). The present study investigated the possible signaling pathways that may mediate the protective effects of zinc in AGE-treated MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 91%

Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Xiong¹,

Liu²,

Liu³

et al. 2015

Molecular Medicine Reports

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Osteoporosis and diabetes have become serious health problems worldwide. Previous studies have suggested that diabetes is associated with osteoporosis and increased fracture risk. However, the mechanism underlying diabetes‑induced osteoporosis remains to be elucidated. Therefore, the present study aimed to examine the mechanism underlying diabetes‑induced osteoporosis, and determine the protective effects of zinc, which is known to be closely associated with osteoporosis and diabetes. The results of the present study demonstrated that zinc inhibited advanced glycation end product (AGE)‑induced MC3T3‑E1 cell apoptosis by attenuating the production of reactive oxygen species, inhibiting caspase‑3 and caspase‑9 activation, and inhibiting the release of cytochrome c from between the mitochondria and the cytosol. Furthermore, zinc was found to protect cells against AGE‑induced apoptosis via the mitogen‑activated protein kinase/extracellular signal‑regulated kinase and phosphoinositide 3‑kinase/AKT signaling pathways. In conclusion, these findings enable a better understanding of the mechanism underlying diabetes‑induced osteoporosis, and may indicate a novel target for its prevention and treatment.

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Section: Discussionmentioning

confidence: 91%

Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Xiong¹,

Liu²,

Liu³

et al. 2015

Molecular Medicine Reports

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“…This disruption leads to oxidative stress by reducing glutathione levels and increasing reactive oxygen species levels in a cell-specific manner [25]. DQ also interferes with signalling pathways, such as by downregulating the Raf/MEK/ERK1/2 and PI3K/Akt pathways in NB4 leukaemia cells [26][27][28]. The mitochondrial damage induced by DQ is an early event in its mechanism of action [26].…”

Section: Dequalinium Chloride (Dq)mentioning

confidence: 99%

Toxic Effects of Penetrating Cations

Sokolov,

Zyrina,

Akimov

et al. 2023

Membranes

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As mitochondria are negatively charged organelles, penetrating cations are used as parts of chimeric molecules to deliver specific compounds into mitochondria. In other words, they are used as electrophilic carriers for such chemical moieties as antioxidants, dyes, etc., to transfer them inside mitochondria. However, unmodified penetrating cations affect different aspects of cellular physiology as well. In this review, we have attempted to summarise the data about the side effects of commonly used natural (e.g., berberine) and artificial (e.g., tetraphenylphosphonium, rhodamine, methylene blue) penetrating cations on cellular physiology. For instance, it was shown that such types of molecules can (1) facilitate proton transport across membranes; (2) react with redox groups of the respiratory chain; (3) induce DNA damage; (4) interfere with pleiotropic drug resistance; (5) disturb membrane integrity; and (6) inhibit enzymes. Also, the products of the biodegradation of penetrating cations can be toxic. As penetrating cations accumulate in mitochondria, their toxicity is mostly due to mitochondrial damage. Mitochondria from certain types of cancer cells appear to be especially sensitive to penetrating cations. Here, we discuss the molecular mechanisms of the toxic effects and the anti-cancer activity of penetrating cations.

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“…At the mitochondrial level, DQ induces a concentration-dependent oxidative stress by decreasing glutathione (GSH) and increasing reactive oxygen species (ROS) levels in a cell type specific manner [21]. The mitochondrial action is coupled with an interference of the drug with different signaling pathways, such as a downregulation of the Raf/MEK/ERK1/2 and PI3K/Akt pathways in NB4 leukemia cells [22][23][24]. The mitochondrial action of the drug is considered an early event of its mechanism of action, leading to cell respiratory damages [22].…”

Section: Dequalinium Chloride (Dq)mentioning

confidence: 99%

Toxic Effects of Penetrating Cations

Sokolov,

Zyrina,

Akimov

et al. 2023

Preprint

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As mitochondria are negatively charged organelles, penetrating cations are used as a part of the chimeric molecules to deliver the specific compounds into mitochondria. However, unmodified penetrating cations affect different aspects of cellular physiology as well. In this review we have attempted to summarize the data about side effects of the commonly used natural (e.gberberine) and artificial (e.g. tetraphenylphosphonium, rhodamine, methylene blue) penetrating cations on cellular physiology. For instance, it was shown that such types of molecules can (1) facilitate proton transport across membranes; (2) react with redox groups of respiratory chain; (3) induce DNA damage; (4) interfere with pleiotropic drug resistance; (5) disturb membrane integrity (6) inhibit the enzymes. Also, the products of the biodegradation of penetrating cations can be toxic. As penetrating cations accumulate in mitochondria, their toxicity is mostly due to the mitochondrial damage. Mitochondria of certain types of cancer cells appear to be especially sensitive to penetrating cations. Here we discuss the molecular mechanisms of the toxic effects and the anti-cancer activity of the penetrating cations.

show abstract

Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways

Cited by 8 publications

References 43 publications

Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Toxic Effects of Penetrating Cations

Toxic Effects of Penetrating Cations

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