Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line

Narayanan, Prasad and Farghadani, Reyhaneh and Nyamathulla, Shaik and Rajarajeswaran, Jayakumar and Thirugnanasampandan, R. and Bhuwaneswari, Gunasekaran (2022) Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line. Journal of Biochemical and Molecular Toxicology, 36 (5). DOI https://doi.org/10.1002/jbt.23008.

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Abstract

Pancreatic cancer is one of the most devastating of all malignancies with poor prognosis and high mortality rates worldwide. Thymoquinone, plumbagin and juglone, which are naturally occurring quinones, have been reported for their promising anticancer effect on different cancer cells. However, their mechanism of action and antimetastatic effects are largely unknown against the human pancreatic cancer cell line (PANC-1). In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay revealed a dose-dependent decrease of viability in quinone-treated PANC-1 cells. In addition, the assessment of changes in cells has demonstrated an occurrence of typical apoptotic morphology in treated PANC-1 cells compared with control. Besides this, the apoptosis induction was further quantitatively confirmed through flow cytometry analysis. Furthermore, thymoquinone, plumbagin and juglone were evaluated for their influence on reactive oxygen species (ROS) generation through 2,7-dichlorofluorescein diacetate (DCFDA) staining and they dramatically increased the intracellular ROS level in treated PANC-1 cells, suggesting the critical role of ROS in their apoptosis induction. This study also demonstrated the wound healing potential of these compounds and inhibited PANC-1 cell migration in a time-dependent manner compared with control. This inhibition was correlated with reduced expression of matrix metalloproteinase-9 (MMP-9) in juglone-treated cells detected through gelatin zymography. In conclusion, thymoquinone, plumbagin and juglone significantly inhibited cell growth and induced ROS-mediated apoptosis in PANC-1 cells. In addition, they could be potent antimetastatic agents due to their anti-migratory effect against PANC-1 human pancreatic cancer cells.

Item Type: Article
Funders: University Malaya Research and Postgraduate Research and Postgraduate Research Grant [Grant No:RG372/15AFR], University Malaya Research and Postgraduate Research and Postgraduate Research Grant [Grant No:PG277-2016A]
Uncontrolled Keywords: Antimetastasis; Anti-migratory; Naphthoquinones; Pancreatic cancer; Quinones
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy
Faculty of Pharmacy > Department of Pharmaceutical Technology
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 05 Oct 2023 01:15
Last Modified: 05 Oct 2023 01:15
URI: http://eprints.um.edu.my/id/eprint/42994

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