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Open AccessArticle

Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib

1
Department of Maxillofacial and Plastic Surgery, Medical University of Bialystok, Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland
2
Department of Otolaryngology, Provincial Hospital in Bialystok, Sklodowskiej-Curie 26, 15-278 Bialystok, Poland
3
Department of Pharmaceutical Analysis, Medical University of Bialystok, Mickiewicza 2D, 15-522 Białystok, Poland
4
Department of Medicinal Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-522 Białystok, Poland
5
Chair and Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
6
Department of Medical Pathomorphology, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 136; https://doi.org/10.3390/cancers12010136
Received: 19 November 2019 / Revised: 18 December 2019 / Accepted: 20 December 2019 / Published: 6 January 2020
Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods: To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results: Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions: Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment. View Full-Text
Keywords: oral cancer; oral squamous cell carcinoma; apoptosis; proline; proline dehydrogenase/oxidase; celecoxib oral cancer; oral squamous cell carcinoma; apoptosis; proline; proline dehydrogenase/oxidase; celecoxib
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Tołoczko-Iwaniuk, N.; Dziemiańczyk-Pakieła, D.; Celińska-Janowicz, K.; Zaręba, I.; Klupczyńska, A.; Kokot, Z.J.; Nowaszewska, B.K.; Reszeć, J.; Borys, J.; Miltyk, W. Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib. Cancers 2020, 12, 136.

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