In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations.

Autor: Al Awadh AA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia., Sakagami H; Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan., Amano S; Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan., Sayed AM; Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.; Department of Pharmacognosy, Collage of Pharmacy, Almaaqal University, Basra, Iraq., Abouelela ME; Pharmacognosy Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt., Alhasaniah AH; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia., Aldabaan N; Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia., Refaey MS; Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufiya, Egypt., Abdelhamid RA; Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut-Branch, Assiut, Egypt., Khalil HMA; Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt., Hamdan DI; Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Menoufia University, Shibin Elkom, Egypt., Abdel-Sattar ES; Department of Medical Microbiology and Immunology, Faculty of Pharmacy, South Valley University, Qena, Egypt., Orabi MAA; Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia.
Jazyk: angličtina
Zdroj: Frontiers in pharmacology [Front Pharmacol] 2024 Jan 18; Vol. 15, pp. 1325272. Date of Electronic Publication: 2024 Jan 18 (Print Publication: 2024).
DOI: 10.3389/fphar.2024.1325272
Abstrakt: Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC 50 = 51.8 and 40.1 μg/mL, respectively), which is relatively the same effect as 5-FU at CC 50 = 69.4 μM and melphalan at CC 50 = 36.3 μM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 μg/mL) exerted morphological changes and induced subG 1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D ( 18 ) and O ( 12 ), and the flavonoid kaempferol ( 11 ). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera 's potential as an affordable source of therapeutic agents for a range of oral malignancies.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AE-B declared a shared affiliation with the author(s) MA and RA to the handling editor at the time of review.
(Copyright © 2024 Al Awadh, Sakagami, Amano, Sayed, Abouelela, Alhasaniah, Aldabaan, Refaey, Abdelhamid, Khalil, Hamdan, Abdel-Sattar and Orabi.)
Databáze: MEDLINE
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