RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines
1,3,4-Oxadiazole derivatives are among the most studied anticancer drugs. Previous studies have analyzed the action of different 1,3,4-oxadiazole derivatives and their effects on cancer cells. This study investigated the characterization of two new compounds named <b>6</b> and <b>1...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11263 |
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| author | Stefano Zoroddu Luca Sanna Valentina Bordoni Weidong Lyu Gabriele Murineddu Gerard A. Pinna Sonia Vanina Forcales Arturo Sala David J. Kelvin Luigi Bagella |
| author_facet | Stefano Zoroddu Luca Sanna Valentina Bordoni Weidong Lyu Gabriele Murineddu Gerard A. Pinna Sonia Vanina Forcales Arturo Sala David J. Kelvin Luigi Bagella |
| author_sort | Stefano Zoroddu |
| collection | DOAJ |
| description | 1,3,4-Oxadiazole derivatives are among the most studied anticancer drugs. Previous studies have analyzed the action of different 1,3,4-oxadiazole derivatives and their effects on cancer cells. This study investigated the characterization of two new compounds named <b>6</b> and <b>14</b> on HeLa and PC-3 cancer cell lines. Based on the previously obtained IC<sub>50</sub>, cell cycle effects were monitored by flow cytometry. RNA sequencing (RNAseq) was performed to identify differentially expressed genes, followed by functional annotation using gene ontology (GO), KEGG signaling pathway enrichment, and protein–protein interaction (PPI) network analyses. The tubulin polymerization assay was used to analyze the interaction of both compounds with tubulin. The results showed that <b>6</b> and <b>14</b> strongly inhibited the proliferation of cancer cells by arresting them in the G2/M phase of the cell cycle. Transcriptome analysis showed that exposure of HeLa and PC-3 cells to the compounds caused a marked reprograming of gene expression. Functional enrichment analysis indicated that differentially expressed genes were significantly enriched throughout the cell cycle and cancer-related biological processes. Furthermore, PPI network, hub gene, and CMap analyses revealed that compounds <b>14</b> and <b>6</b> shared target genes with established microtubule inhibitors, indicating points of similarity between the two molecules and microtubule inhibitors in terms of the mechanism of action. They were also able to influence the polymerization process of tubulin, suggesting the potential of these new compounds to be used as efficient chemotherapeutic agents. |
| first_indexed | 2024-03-11T01:01:21Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:01:21Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1d9bc7826aa64ecb8baf61a35f9155c02023-11-18T19:36:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141126310.3390/ijms241411263RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell LinesStefano Zoroddu0Luca Sanna1Valentina Bordoni2Weidong Lyu3Gabriele Murineddu4Gerard A. Pinna5Sonia Vanina Forcales6Arturo Sala7David J. Kelvin8Luigi Bagella9Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDivision of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, Shantou 515031, ChinaDepartment of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, ItalyDepartment of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, ItalyDepartment of Pathology and Experimental Therapeutics, School of Medicine, Health Science Campus of Bellvitge, University of Barcelona, Carrer de la Feixa Llarga, s/n, Hospitalet de Llobregat, 08907 Barcelona, SpainCentre for Inflammation Research and Translational Medicine (CIRTM), Department of Life Sciences, Brunel University, London UB8 3PH, UKDivision of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, Shantou 515031, ChinaDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy1,3,4-Oxadiazole derivatives are among the most studied anticancer drugs. Previous studies have analyzed the action of different 1,3,4-oxadiazole derivatives and their effects on cancer cells. This study investigated the characterization of two new compounds named <b>6</b> and <b>14</b> on HeLa and PC-3 cancer cell lines. Based on the previously obtained IC<sub>50</sub>, cell cycle effects were monitored by flow cytometry. RNA sequencing (RNAseq) was performed to identify differentially expressed genes, followed by functional annotation using gene ontology (GO), KEGG signaling pathway enrichment, and protein–protein interaction (PPI) network analyses. The tubulin polymerization assay was used to analyze the interaction of both compounds with tubulin. The results showed that <b>6</b> and <b>14</b> strongly inhibited the proliferation of cancer cells by arresting them in the G2/M phase of the cell cycle. Transcriptome analysis showed that exposure of HeLa and PC-3 cells to the compounds caused a marked reprograming of gene expression. Functional enrichment analysis indicated that differentially expressed genes were significantly enriched throughout the cell cycle and cancer-related biological processes. Furthermore, PPI network, hub gene, and CMap analyses revealed that compounds <b>14</b> and <b>6</b> shared target genes with established microtubule inhibitors, indicating points of similarity between the two molecules and microtubule inhibitors in terms of the mechanism of action. They were also able to influence the polymerization process of tubulin, suggesting the potential of these new compounds to be used as efficient chemotherapeutic agents.https://www.mdpi.com/1422-0067/24/14/11263oxadiazolecancermicrotubulechemotherapyRNAseq |
| spellingShingle | Stefano Zoroddu Luca Sanna Valentina Bordoni Weidong Lyu Gabriele Murineddu Gerard A. Pinna Sonia Vanina Forcales Arturo Sala David J. Kelvin Luigi Bagella RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines International Journal of Molecular Sciences oxadiazole cancer microtubule chemotherapy RNAseq |
| title | RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines |
| title_full | RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines |
| title_fullStr | RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines |
| title_full_unstemmed | RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines |
| title_short | RNAseq Analysis of Novel 1,3,4-Oxadiazole Chalcogen Analogues Reveals Anti-Tubulin Properties on Cancer Cell Lines |
| title_sort | rnaseq analysis of novel 1 3 4 oxadiazole chalcogen analogues reveals anti tubulin properties on cancer cell lines |
| topic | oxadiazole cancer microtubule chemotherapy RNAseq |
| url | https://www.mdpi.com/1422-0067/24/14/11263 |
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