ITRACONAZOLE: A PROMISING REPURPOSED CHEMOTHERAPEUTIC AGENT FOR TONGUE CARCINOMA | ||||
| Egyptian Journal of Histology | ||||
| Articles in Press, Accepted Manuscript, Available Online from 14 March 2023 | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ejh.2023.188661.1846 | ||||
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| Authors | ||||
Hala El-kammar 1; Mohamed Ammar2; Iten Fawzy 3; Dina Kashkoush 4; Nermeen Afifi  5
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| 1Department of Oral Pathology, Faculty of Oral and Dental Medicine, Future University in Egypt. | ||||
| 2Department of Dental Biomaterials, Faculty of Oral and Dental Medicine, Future University in Egypt, Cairo, Egypt | ||||
| 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt | ||||
| 4Department of Oral Biology, Faculty of Dentistry, Ain-Shams University, Cairo, Egypt. | ||||
| 5Assistant Professor of Oral pathology,Faculty of Dentistry Ain Shams University and Misr International University, Cairo, Egypt | ||||
| Abstract | ||||
| Researching novel chemotherapeutic agents is desirable but it is not ideal in terms of cost and time, hence, repurposing current drugs for cancer treatment is becoming more appealing. Itraconazole (ITZ), traditionally an anti-fungal drug has been re-purposed recently as an anticancer agent for many cancer types. There is continuous bidirectional and intricate crosstalk between cancer-associated fibroblasts (CAFs) and cancer cells. Most emerging trends in CAF biology draw attention to CAF-secreted factors as druggable targets. PI3/AKT signaling has been linked to both α-SMA and TGF-β expressions and CAFs differentiation and is a key player in, chemotherapeutic resistance. Objectives: This study aimed to correlate the immunohistochemical expression of α-SMA as a marker for CAF and TGF-β with tumor grade and lymph node involvement in tongue squamous cell carcinoma (TSCC) specimens and to evaluate the effect of ITZ on invasion and migration of TSCC cell line. Materials and Methods: Immunohistochemical expression of α-SMA and TGF-β in twenty-four samples of different grades of TSCC and clinical lymph node involvement were evaluated retrospectively. Molecular docking of ITZ with PI3/AKT was performed and its effect on SCC-25 cell line cultured in medium obtained from co-culture of WI-38 (normal fibroblast) and SCC-25 cell lines was assessed. Expression of α-SMA, TGF-β, SNAIL and VEGF genes as well as invasion and migration ability were evaluated. Results: Immunohistochemical expression of α-SMA and TGF-β was significantly higher in cases exhibiting lymph node involvement. ITZ interacted strongly with PI3/AKT proteins ITZ-treated group showed significantly lower migration and invasion ability as well as α-SMA, TGF-β, SNAIL and VEGF expressions compared to control group. Conclusion: ITZ was able to inhibit invasion and migration of TSCC cell line in vitro. | ||||
| Keywords | ||||
| cancer associated fibroblasts; α-SMA; TGF-β; SNAIL; PI3/AKT | ||||
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