Cetylpyridinium Chloride Inhibits Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Formation

Zheng, Ting; Chen, Ling; Noh, A Long Sae Mi; Yim, Mijung

doi:10.1248/bpb.b12-00460

Cited by 12 publications

(5 citation statements)

References 20 publications

(23 reference statements)

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“…23 Also, it has been reported that CPC inhibited osteoclast differentiation in a dose-response way. 32 All these adverse effects of CPC must be considered in clinical applications to treat chronical diseases.…”

Section: Discussionmentioning

confidence: 99%

Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way

García-Cuéllar

Hernandez-Delgadillo

Solís-Soto

et al. 2022

Journal of Applied Biomaterials & Functional Materials

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Objective: Analyze the antitumor capacity of cetylpyridinium chloride (CPC) on human breast tumor cells, and the possible action mechanism. Material and methods: The human breast tumor cells MCF-7 and no-tumor breast cells MCF-10A were exposed to CPC under various condition (concentration and duration). Cell viability was measured with MTT assay, the LIVE/DEAD assay, and fluorescence microscopy. Membrane permeability after CPC exposure was evaluated by Calcein AM assay, mitochondrial morphology with a MitoView staining, and genotoxicity with the comet assay and fluorescence microscopy. Results: CPC was cytotoxic to both MCF-7 and MCF-10A as of a 24-h exposure to 0.1 µM. Cytotoxicity was dose-dependent and reached 91% for MCF-7 and 78% for MCF-10A after a 24-h exposure to 100 µM CPC, which outperformed the positive control doxorubicin in effectiveness and selectivity. The LD50 of CPC on was 6 µM for MCF-7 and 8 µM for MCF-10A, yielding a selectivity index of 1.41. A time response analysis revealed 64% dead cells after only 5 min of exposure to 100 µM CPC. With respect to the action mechanisms, the comet assay did not reveal genome fragmentation. On the other hand, membrane damage was dose-dependent and may also affect mitochondrial morphology. Conclusion: Cetylpyridinium chloride inhibits MCF-7 cell growing in a non-selective way as of 5 min of exposure. The action mechanism of CPC on tumor cells involves cell membrane damage without change neither mitochondrial morphology nor genotoxicity.

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Section: Discussionmentioning

confidence: 99%

Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way

García-Cuéllar

Hernandez-Delgadillo

Solís-Soto

et al. 2022

Journal of Applied Biomaterials & Functional Materials

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“…Blimp1 is a master protein regulating the transcriptional network that improves B cell terminal differentiation. Bcl6 functions opposite to Blimp1 in regulating differentiation of B lymphocytes, and it can inhibit and block terminal differentiation of B lymphocytes (20)(21)(22)(23). High expression of Bcl6 in B cell lymphoma tissues has been associated with poor differentiation grade (24,25).…”

Section: Influence Onblimp1 and Bcl6 Expression May Be Involved In MDmentioning

confidence: 99%

Mda-7/IL-24 induces the differentiation of B cell lymphoma via activation of the P38 mitogen activated protein kinase signaling pathway

Yang

Zhao

et al. 2017

Molecular Medicine Reports

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Interleukin 24 (IL‑24) is a unique cytokine encoded by the melanoma differentiation associated gene‑7 (Mda‑7), and was first discovered inhuman melanoma cells. Exogenous Mda‑7/IL‑24 has been shown to inhibit the proliferation and invasion of a broad spectrum of human cancer cells, but its effect on the differentiation of B cell lymphoma is not yet clear. To the best of our knowledge, the present study demonstrated for the first time that overexpressing Mda‑7/IL‑24 can induce differentiation in human B cell lymphomacells, and the underlying mechanism was investigated. The proliferation of stable Mda‑7/IL‑24 overexpressing Raji and Daudi cells was assessed by the MTS method. The immunophenotype, apoptosis level and cell cycle distribution of Raji and Daudi cells were analyzed by flow cytometry. The expression of PR domain zinc finger protein 1 (Blimp1) and B‑cell lymphoma 6 (Bcl6) were analyzed by western blotting. Additionally, western blotting assay was also performed to study the effect of Mda‑7/IL‑24 on the activity of the P38 mitogen activated protein kinase (MAPK) signaling pathway in Raji and Daudi cells. Proliferation of Raji and Daudi cells overexpressing Mda‑7/IL‑24 was inhibited significantly, compared with those of parent cells and cells transfected with the empty vector alone. Apoptosis was not involved in the proliferation inhibition, while the cell cycle was arrested in G1 phase in the Raji and Daudi cells overexpressing Mda‑7/IL‑24. Overexpressing Mda‑7/IL‑24 resulted in a significantly decreased expression of cluster of differentiation (CD)10, and increased expression of CD45 and CD138 in the cell surface of Raji and Daudi cells. The expression of Blimp1 was upregulated, while the levels of Bcl6 protein was downregulated, in Raji and Daudi cells overexpressing Mda‑7/IL‑24. Furthermore, the activities of the P38 MAPK signaling pathway in lymphoma cells were upregulated. These results indicated that Mda‑7/IL‑24 could induce terminal differentiation of B lymphoma cells by regulating the expression of Blimp1 and Bcl6 via altering the P38 MAPK signaling pathway, suggesting that Mda‑7/IL‑24 may therefore be a potential differentiation therapeutic agent to be applied in clinical treatment of B cell lymphoma.

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“…CPC helps to fight plaque (Sreenivasan et al ., 2013), gingivitis (Teng et al ., 2016), halitosis (Yaegaki and Sanada, 1992), and bacterial infections (Schaeffer et al ., 2011; Latimer et al ., 2015). Due to these oral care properties, including potential effects on bone signaling (Zheng et al ., 2013), the addition of CPC to dental restorations is also being explored (Tomino et al ., 2016; Yamamoto et al ., 2022). CPC is used in numerous other cosmetics (hair coloring and styling products, deodorant, hair conditioners, and cosmetic biocides) and in the active pharmaceutical industry as an intermediate (PubChem).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Antimicrobial Agent Cetylpyridinium Chloride Mitochondrial Toxicity in Rodent and Primary Human Cells: Super-resolution Microscopy Reveals Nanostructural Disruption

Weller

Burnell

Aho

et al. 2022

Preprint

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People are exposed to high concentrations of antibacterial agent cetylpyridinium chloride (CPC) via personal care and food products, despite little information regarding CPC effects on eukaryotes. CPC is used as an antibacterial agent via a detergent mechanism when above ~600-900 μM. While three previous studies suggested CPC mitochondrial toxicity, this phenomenon is not well-studied. Here, we show that low-micromolar CPC inhibits mitochondrial ATP production in primary human keratinocytes, mouse NIH-3T3 fibroblasts, and rat RBL-2H3 immune mast cells, in galactose media, which causes cells to produce ATP via mitochondria. ATP inhibition via CPC (EC50 1.7 μM) is nearly as potent as that caused by canonical mitotoxicant CCCP (EC50 1.2 μM). CPC inhibition of oxygen consumption rate (OCR) tracks with that of ATP: OCR is halved due to 1.75 μM CPC in RBL-2H3 cells and 1.25 μM in primary human keratinocytes. Here we demonstrate that CPC is more potent as a mitotoxicant than as an immune mast cell signaling inhibitor, an effect published previously. Mitochondrial [Ca2+] changes can cause mitochondrial dysfunction. Here we show, using a novel plate reader assay with reporter CEPIA2mt, that CPC causes mitochondrial Ca2+ efflux from mast cells via an ATP-inhibition mechanism. Using super-resolution microscopy (fluorescence photoactivation localization) in live cells, we have discovered that CPC causes mitochondrial nanostructural defects in fibroblasts, including the formation of spherical structures with donut-like cross section, as quantified by novel Fourier transform analysis. This work reveals CPC as a mitotoxicant despite widespread use, highlighting the importance of further research into its toxicological safety.

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Cetylpyridinium Chloride Inhibits Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Formation

Cited by 12 publications

References 20 publications

Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way

Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way

Mda-7/IL-24 induces the differentiation of B cell lymphoma via activation of the P38 mitogen activated protein kinase signaling pathway

Mechanisms of Antimicrobial Agent Cetylpyridinium Chloride Mitochondrial Toxicity in Rodent and Primary Human Cells: Super-resolution Microscopy Reveals Nanostructural Disruption

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