A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment
Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific ta...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Applied Sciences |
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| Online Access: | https://www.mdpi.com/2076-3417/11/19/9139 |
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| author | Maria Stefania Sinicropi Cinzia Tavani Camillo Rosano Jessica Ceramella Domenico Iacopetta Alexia Barbarossa Lara Bianchi Alice Benzi Massimo Maccagno Marco Ponassi Domenico Spinelli Giovanni Petrillo |
| author_facet | Maria Stefania Sinicropi Cinzia Tavani Camillo Rosano Jessica Ceramella Domenico Iacopetta Alexia Barbarossa Lara Bianchi Alice Benzi Massimo Maccagno Marco Ponassi Domenico Spinelli Giovanni Petrillo |
| author_sort | Maria Stefania Sinicropi |
| collection | DOAJ |
| description | Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues <b>1</b>–<b>8</b>. Among them, 2-nitrocarbazole <b>1</b> exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC<sub>50</sub> values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound <b>1</b> did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound <b>1</b> to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay. |
| first_indexed | 2024-03-10T07:06:14Z |
| format | Article |
| id | doaj.art-f00f52989bf840a2adb2ea9439a2a6d7 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T07:06:14Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-f00f52989bf840a2adb2ea9439a2a6d72023-11-22T15:48:19ZengMDPI AGApplied Sciences2076-34172021-10-011119913910.3390/app11199139A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer TreatmentMaria Stefania Sinicropi0Cinzia Tavani1Camillo Rosano2Jessica Ceramella3Domenico Iacopetta4Alexia Barbarossa5Lara Bianchi6Alice Benzi7Massimo Maccagno8Marco Ponassi9Domenico Spinelli10Giovanni Petrillo11Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, ItalyProteomics and Mass Spectrometry Unit, IRCCS Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genoa, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70126 Bari, ItalyDepartment of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, ItalyProteomics and Mass Spectrometry Unit, IRCCS Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genoa, ItalyDepartment of Chemistry ‘G. Ciamician’, Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna, ItalyDepartment of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, ItalyBreast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues <b>1</b>–<b>8</b>. Among them, 2-nitrocarbazole <b>1</b> exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC<sub>50</sub> values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound <b>1</b> did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound <b>1</b> to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.https://www.mdpi.com/2076-3417/11/19/9139carbazolesellipticinetubulinbreast cancerapoptosisdocking simulations |
| spellingShingle | Maria Stefania Sinicropi Cinzia Tavani Camillo Rosano Jessica Ceramella Domenico Iacopetta Alexia Barbarossa Lara Bianchi Alice Benzi Massimo Maccagno Marco Ponassi Domenico Spinelli Giovanni Petrillo A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment Applied Sciences carbazoles ellipticine tubulin breast cancer apoptosis docking simulations |
| title | A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment |
| title_full | A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment |
| title_fullStr | A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment |
| title_full_unstemmed | A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment |
| title_short | A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment |
| title_sort | nitrocarbazole as a new microtubule targeting agent in breast cancer treatment |
| topic | carbazoles ellipticine tubulin breast cancer apoptosis docking simulations |
| url | https://www.mdpi.com/2076-3417/11/19/9139 |
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