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

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...

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Main Authors: Narayanan, Prasad, Farghadani, Reyhaneh, Nyamathulla, Shaik, Rajarajeswaran, Jayakumar, Thirugnanasampandan, R., Bhuwaneswari, Gunasekaran
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Published: WILEY 2022
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Online Access:http://eprints.um.edu.my/42994/
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spelling my.um.eprints.429942023-10-05T01:15:40Z http://eprints.um.edu.my/42994/ Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line Narayanan, Prasad Farghadani, Reyhaneh Nyamathulla, Shaik Rajarajeswaran, Jayakumar Thirugnanasampandan, R. Bhuwaneswari, Gunasekaran RS Pharmacy and materia medica 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. WILEY 2022-05 Article PeerReviewed 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 <https://doi.org/10.1002/jbt.23008>. 10.1002/jbt.23008
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic RS Pharmacy and materia medica
spellingShingle RS Pharmacy and materia medica
Narayanan, Prasad
Farghadani, Reyhaneh
Nyamathulla, Shaik
Rajarajeswaran, Jayakumar
Thirugnanasampandan, R.
Bhuwaneswari, Gunasekaran
Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
description 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.
format Article
author Narayanan, Prasad
Farghadani, Reyhaneh
Nyamathulla, Shaik
Rajarajeswaran, Jayakumar
Thirugnanasampandan, R.
Bhuwaneswari, Gunasekaran
author_facet Narayanan, Prasad
Farghadani, Reyhaneh
Nyamathulla, Shaik
Rajarajeswaran, Jayakumar
Thirugnanasampandan, R.
Bhuwaneswari, Gunasekaran
author_sort Narayanan, Prasad
title Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
title_short Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
title_full Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
title_fullStr Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
title_full_unstemmed Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
title_sort natural quinones induce ros-mediated apoptosis and inhibit cell migration in panc-1 human pancreatic cancer cell line
publisher WILEY
publishDate 2022
url http://eprints.um.edu.my/42994/
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