Effect of hinokitiol in ameliorating oral cancer: in vitro and in silico evidences.

Autor: Roy A; Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, SIMATS, Chennai, Tamil Nadu, 600077, India., Cheriyan BV; Department of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, SIMATS, Chennai, Tamil Nadu, 602105, India. lallybinoy@gmail.com., Perumal E; Cancer Genomics lab, Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, SIMATS, Chennai, Tamil Nadu, 602105, India., Rengasamy KR; Laboratory of Natural Products and Medicinal Chemistry (LNPMC), Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, SIMATS, Chennai, Tamil Nadu, 602105, India., Anandakumar S; Department of Microbiology, Dr. ALM Post Graduate Institute of Basic Medical Science, University of Madras, Chennai, Tamil Nadu, 600113, India.
Jazyk: angličtina
Zdroj: Odontology [Odontology] 2024 Nov 14. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1007/s10266-024-01020-1
Abstrakt: The study aimed to evaluate the anticancer potential of hinokitiol in treating oral cancer by using in vitro models and examining its interaction with the Pim-1 protein through in silico methods. Hinokitiol was applied to KB-1 oral squamous carcinoma cells, where the half-maximal inhibitory concentrations (IC 50 ) was determined. Morphologic changes in treated cells were observed using phase contrast microscopy, while acridine orange/ethidium bromide (AO/EB) staining was used to assess nuclear changes and apoptosis. Flow cytometry was employed to analyze the cell-cycle progression. Given the high expression of Pim-1 in oral squamous carcinoma cells, molecular docking and simulation were performed to evaluate hinokitiol's binding affinity and stability with the Pim-1 protein. To compare its effects, hinokitiol was also tested on non-cancerous pre-adipocytes (3T3-L1), providing insights into its selective cytotoxicity between healthy and cancerous cells. Hinokitiol treatment resulted in cytotoxic effects on KB-1 oral squamous carcinoma cells, with an IC 50 of 30 µg/mL after 24 and 48 hs of exposure. Morphologic studies showed reduced cell population and density. In contrast, hinokitiol exhibited lower toxicity and caused fewer morphological changes in non-cancerous 3T3-L1 pre-adipocytes. Apoptosis was confirmed through acridine orange/ethidium bromide staining, while flow cytometry revealed cell-cycle arrest in the Synthesis phase (S) and Gap 2 phase/ Mitosis Phase (G2/M) phases. Molecular docking showed strong binding of hinokitiol to Pim-1, and simulations confirmed the interaction's stability. These findings suggest hinokitiol selectively targets cancer cells and effectively inhibit Pim-1, supporting its potential as an oral cancer treatment.
Competing Interests: Declarations Conflict of interest No conflict of interest was declared by the authors.
(© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)
Databáze: MEDLINE
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