Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells
We investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry,...
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/15/3867 |
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| author | Maria Condello Gloria D’Avack Rosa Vona Enrico Pierluigi Spugnini Licia Scacco Stefania Meschini |
| author_facet | Maria Condello Gloria D’Avack Rosa Vona Enrico Pierluigi Spugnini Licia Scacco Stefania Meschini |
| author_sort | Maria Condello |
| collection | DOAJ |
| description | We investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry, demonstrating that both lines were intrinsically resistant. After establishing the optimal dose of mitomycin C (MMC) to be used, in combination with EP, we showed, by both MTT assay and optical and electron scanning microscopy, the potentiating cytotoxic effect of EP with MMC compared to single treatments. Flow cytometry showed that the cytotoxicity of EP + MMC was due to the induction of apoptosis. In addition to verifying the release of cytochrome C in EP + MMC samples, we performed an expression analysis of caspase-3, caspase-9, Akt, pAkt, HMGB1, LC3I, LC3II, p62, Beclin1, and associated proteins with both apoptotic and autophagic phenomena. Our results were confirmed by two veterinary patients in whom the EP + MMC combination was used to control margins after the resection of corneal squamous carcinoma. In conclusion, we affirmed that the effect for which EP enhances MMC treatment is due to the inhibition of the autophagic process induced by the drug in favor of apoptosis. |
| first_indexed | 2024-03-10T09:16:46Z |
| format | Article |
| id | doaj.art-2bf8f08c43654cadaf2999fd20594ce3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:16:46Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2bf8f08c43654cadaf2999fd20594ce32023-11-22T05:29:17ZengMDPI AGCancers2072-66942021-07-011315386710.3390/cancers13153867Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma CellsMaria Condello0Gloria D’Avack1Rosa Vona2Enrico Pierluigi Spugnini3Licia Scacco4Stefania Meschini5National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyCenter for Gender-Specific Medicine, National Institute of Health, 00161 Rome, ItalyBiopulse S.r.l., 80132 Naples, ItalyEquivet Roma Hospital, 00134 Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyWe investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry, demonstrating that both lines were intrinsically resistant. After establishing the optimal dose of mitomycin C (MMC) to be used, in combination with EP, we showed, by both MTT assay and optical and electron scanning microscopy, the potentiating cytotoxic effect of EP with MMC compared to single treatments. Flow cytometry showed that the cytotoxicity of EP + MMC was due to the induction of apoptosis. In addition to verifying the release of cytochrome C in EP + MMC samples, we performed an expression analysis of caspase-3, caspase-9, Akt, pAkt, HMGB1, LC3I, LC3II, p62, Beclin1, and associated proteins with both apoptotic and autophagic phenomena. Our results were confirmed by two veterinary patients in whom the EP + MMC combination was used to control margins after the resection of corneal squamous carcinoma. In conclusion, we affirmed that the effect for which EP enhances MMC treatment is due to the inhibition of the autophagic process induced by the drug in favor of apoptosis.https://www.mdpi.com/2072-6694/13/15/3867electrochemotherapymitomycin Csquamous carcinoma cell linesdrug resistanceapoptosisautophagy |
| spellingShingle | Maria Condello Gloria D’Avack Rosa Vona Enrico Pierluigi Spugnini Licia Scacco Stefania Meschini Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells Cancers electrochemotherapy mitomycin C squamous carcinoma cell lines drug resistance apoptosis autophagy |
| title | Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells |
| title_full | Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells |
| title_fullStr | Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells |
| title_full_unstemmed | Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells |
| title_short | Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells |
| title_sort | electrochemotherapy with mitomycin c potentiates apoptosis death by inhibiting autophagy in squamous carcinoma cells |
| topic | electrochemotherapy mitomycin C squamous carcinoma cell lines drug resistance apoptosis autophagy |
| url | https://www.mdpi.com/2072-6694/13/15/3867 |
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