Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy
Polo-like-kinase-1 (PLK-1) is a serine/threonine kinase that regulates the cell cycle and acts as an oncogene in multiple cancers, including oral squamous cell carcinoma (OSCC). The loss of PLK-1 can inhibit growth and induce apoptosis, making it an attractive therapeutic target in OSCC. We evaluate...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/503 |
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| author | Subhanwita Sarkar Ayan Chanda Rutvij A. Khanolkar Meghan Lambie Laurie Ailles Scott V. Bratman Aru Narendran Pinaki Bose |
| author_facet | Subhanwita Sarkar Ayan Chanda Rutvij A. Khanolkar Meghan Lambie Laurie Ailles Scott V. Bratman Aru Narendran Pinaki Bose |
| author_sort | Subhanwita Sarkar |
| collection | DOAJ |
| description | Polo-like-kinase-1 (PLK-1) is a serine/threonine kinase that regulates the cell cycle and acts as an oncogene in multiple cancers, including oral squamous cell carcinoma (OSCC). The loss of PLK-1 can inhibit growth and induce apoptosis, making it an attractive therapeutic target in OSCC. We evaluated the efficacy of PLK-1 inhibitors as novel, targeted therapeutics in OSCC. PLK-1 inhibition using BI6727 (volasertib) was found to affect cell death at low nanomolar concentrations in most tested OSCC cell lines, but not in normal oral keratinocytes. In cell lines resistant to volasertib alone, pre-treatment with radiotherapy followed by volasertib reduced cell viability and induced apoptosis. The combinatorial efficacy of volasertib and radiotherapy was replicated in xenograft mouse models. These findings highlight the potential of adding PLK-1 inhibitors to adjuvant therapy regimens in OSCC. |
| first_indexed | 2024-04-24T18:32:32Z |
| format | Article |
| id | doaj.art-9c56982e74b64f5faa7f48ce5af435cd |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:32:32Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-9c56982e74b64f5faa7f48ce5af435cd2024-03-27T13:22:34ZengMDPI AGBiomedicines2227-90592024-02-0112350310.3390/biomedicines12030503Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation TherapySubhanwita Sarkar0Ayan Chanda1Rutvij A. Khanolkar2Meghan Lambie3Laurie Ailles4Scott V. Bratman5Aru Narendran6Pinaki Bose7Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, CanadaDepartment of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaPolo-like-kinase-1 (PLK-1) is a serine/threonine kinase that regulates the cell cycle and acts as an oncogene in multiple cancers, including oral squamous cell carcinoma (OSCC). The loss of PLK-1 can inhibit growth and induce apoptosis, making it an attractive therapeutic target in OSCC. We evaluated the efficacy of PLK-1 inhibitors as novel, targeted therapeutics in OSCC. PLK-1 inhibition using BI6727 (volasertib) was found to affect cell death at low nanomolar concentrations in most tested OSCC cell lines, but not in normal oral keratinocytes. In cell lines resistant to volasertib alone, pre-treatment with radiotherapy followed by volasertib reduced cell viability and induced apoptosis. The combinatorial efficacy of volasertib and radiotherapy was replicated in xenograft mouse models. These findings highlight the potential of adding PLK-1 inhibitors to adjuvant therapy regimens in OSCC.https://www.mdpi.com/2227-9059/12/3/503OSCCpolo-like-kinase-1γ-radiation therapyvolasertib |
| spellingShingle | Subhanwita Sarkar Ayan Chanda Rutvij A. Khanolkar Meghan Lambie Laurie Ailles Scott V. Bratman Aru Narendran Pinaki Bose Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy Biomedicines OSCC polo-like-kinase-1 γ-radiation therapy volasertib |
| title | Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy |
| title_full | Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy |
| title_fullStr | Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy |
| title_full_unstemmed | Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy |
| title_short | Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy |
| title_sort | targeting oral squamous cell carcinoma with combined polo like kinase 1 inhibitors and γ radiation therapy |
| topic | OSCC polo-like-kinase-1 γ-radiation therapy volasertib |
| url | https://www.mdpi.com/2227-9059/12/3/503 |
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