A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC
In tumors, the multi drug resistance phenomenon may occur through the efflux of chemotherapeutic drugs out of cancer cells, impeding their accumulation, and eventually reducing their toxicity. This process is mediated by transporters overexpressed in the plasma membranes of tumor cells, among which...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/989 |
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| author | Maria Pia Adorni Maricla Galetti Silvia La Monica Matteo Incerti Alessandro Ruffoni Lisa Elviri Ilaria Zanotti Bianca Papotti Delia Cavallo Roberta Alfieri Pier Giorgio Petronini Franco Bernini |
| author_facet | Maria Pia Adorni Maricla Galetti Silvia La Monica Matteo Incerti Alessandro Ruffoni Lisa Elviri Ilaria Zanotti Bianca Papotti Delia Cavallo Roberta Alfieri Pier Giorgio Petronini Franco Bernini |
| author_sort | Maria Pia Adorni |
| collection | DOAJ |
| description | In tumors, the multi drug resistance phenomenon may occur through the efflux of chemotherapeutic drugs out of cancer cells, impeding their accumulation, and eventually reducing their toxicity. This process is mediated by transporters overexpressed in the plasma membranes of tumor cells, among which is the P-glycoprotein/multidrug resistance 1/ATP-binding cassette B1 (P-gp/MDR1/ABCB1). The aim of this study was to explore the effect of a new molecule, called AIF-1, on ABCB1 activity. In a cellular model of non-small cell lung cancer (NSCLC), AIF-1 significantly inhibited ABCB1 activity, which was evaluated by the fluorimetric measurement of the intracellular accumulation of calcein. AIF-1 also significantly increased the intracellular content of doxorubicin, which was evaluated by confocal microscopy and LC-MS/MS analysis. This effect translated to higher cytotoxicity of doxorubicin and reduced cellular proliferation. Finally, in a murine xenograft model, the tumor volume increased by 267% and 148% on average in mice treated with vehicle and doxorubicin alone, respectively. After the co-administration of doxorubicin with AIF-1, tumor volume increased by only 13.4%. In conclusion, these results suggest enhancement of the efficacy of the chemotherapeutic drug doxorubicin by AIF-1, laying the basis for the future development of new ABCB1 inhibitors for tumor treatment. |
| first_indexed | 2024-03-09T12:27:08Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:27:08Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c4a168c05a1c44a69fa8b60cea74d82a2023-11-30T22:33:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124298910.3390/ijms24020989A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLCMaria Pia Adorni0Maricla Galetti1Silvia La Monica2Matteo Incerti3Alessandro Ruffoni4Lisa Elviri5Ilaria Zanotti6Bianca Papotti7Delia Cavallo8Roberta Alfieri9Pier Giorgio Petronini10Franco Bernini11Department of Medicine and Surgery, University of Parma, 43125 Parma, ItalyDepartment of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL—Italian Workers’ Compensation Authority, Monte Porzio Catone, 00078 Rome, ItalyDepartment of Medicine and Surgery, University of Parma, 43125 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyInstitute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056 Aachen, GermanyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyDepartment of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL—Italian Workers’ Compensation Authority, Monte Porzio Catone, 00078 Rome, ItalyDepartment of Medicine and Surgery, University of Parma, 43125 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43125 Parma, ItalyDepartment of Food and Drug, University of Parma, 43124 Parma, ItalyIn tumors, the multi drug resistance phenomenon may occur through the efflux of chemotherapeutic drugs out of cancer cells, impeding their accumulation, and eventually reducing their toxicity. This process is mediated by transporters overexpressed in the plasma membranes of tumor cells, among which is the P-glycoprotein/multidrug resistance 1/ATP-binding cassette B1 (P-gp/MDR1/ABCB1). The aim of this study was to explore the effect of a new molecule, called AIF-1, on ABCB1 activity. In a cellular model of non-small cell lung cancer (NSCLC), AIF-1 significantly inhibited ABCB1 activity, which was evaluated by the fluorimetric measurement of the intracellular accumulation of calcein. AIF-1 also significantly increased the intracellular content of doxorubicin, which was evaluated by confocal microscopy and LC-MS/MS analysis. This effect translated to higher cytotoxicity of doxorubicin and reduced cellular proliferation. Finally, in a murine xenograft model, the tumor volume increased by 267% and 148% on average in mice treated with vehicle and doxorubicin alone, respectively. After the co-administration of doxorubicin with AIF-1, tumor volume increased by only 13.4%. In conclusion, these results suggest enhancement of the efficacy of the chemotherapeutic drug doxorubicin by AIF-1, laying the basis for the future development of new ABCB1 inhibitors for tumor treatment.https://www.mdpi.com/1422-0067/24/2/989multidrug resistance (MDR)ATP-binding cassette B1 (ABCB1)lung cancerNSCLCdoxorubicin |
| spellingShingle | Maria Pia Adorni Maricla Galetti Silvia La Monica Matteo Incerti Alessandro Ruffoni Lisa Elviri Ilaria Zanotti Bianca Papotti Delia Cavallo Roberta Alfieri Pier Giorgio Petronini Franco Bernini A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC International Journal of Molecular Sciences multidrug resistance (MDR) ATP-binding cassette B1 (ABCB1) lung cancer NSCLC doxorubicin |
| title | A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC |
| title_full | A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC |
| title_fullStr | A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC |
| title_full_unstemmed | A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC |
| title_short | A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC |
| title_sort | new abcb1 inhibitor enhances the anticancer effect of doxorubicin in both in vitro and in vivo models of nsclc |
| topic | multidrug resistance (MDR) ATP-binding cassette B1 (ABCB1) lung cancer NSCLC doxorubicin |
| url | https://www.mdpi.com/1422-0067/24/2/989 |
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