Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers

Worldwide, hepatocellular carcinoma (HCC) is considered the sixth most prevalent cancer and ranked third in causes leading to death. Pterostilbene (PTE), a dimethylated analog of resveratrol, is a phytochemical found in fruits such as blueberries and grapes, and is known for its anticancer effect. T...

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Main Authors: Mahmoud I. Khalil, Alaa F. Agamy, Salma S. Elshewemi, Ahmed S. Sultan, Nabila E. Abdelmeguid
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Saudi Journal of Biological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319562X23001626
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author Mahmoud I. Khalil
Alaa F. Agamy
Salma S. Elshewemi
Ahmed S. Sultan
Nabila E. Abdelmeguid
author_facet Mahmoud I. Khalil
Alaa F. Agamy
Salma S. Elshewemi
Ahmed S. Sultan
Nabila E. Abdelmeguid
author_sort Mahmoud I. Khalil
collection DOAJ
description Worldwide, hepatocellular carcinoma (HCC) is considered the sixth most prevalent cancer and ranked third in causes leading to death. Pterostilbene (PTE), a dimethylated analog of resveratrol, is a phytochemical found in fruits such as blueberries and grapes, and is known for its anticancer effect. The current study intended to investigate the effect of PTE on HepG2 cells. Cell viability, colony-forming potential, lipid peroxidation, catalase enzyme (CAT), superoxide dismutase (SOD), and caspase 3 activities, histone release, and expression levels of mTOR, S6K1, p53, and STAT3 proteins were assessed in PTE-treated HepG2 cells. In addition, the cellular and ultrastructural alterations were evaluated by light and transmission electron microscopy. PTE induced a significant reduction in HepG2 viability in a dose-dependent manner (IC50 of PTE = 74 ± 6 μM), accompanied by a decrease in colony formation potential. PTE-treated cancer cells exhibited a decrease in lipid peroxidation and CAT activity, and an increase in histone release, caspase-3, and SOD activities. Ultrastructurally, PTE-treated cells exhibited notable cell shrinkage, reduced number of filopodia, increased vacuolization, apoptotic bodies, accumulation of lipid droplets, enlarged mitochondria, dilated endoplasmic reticulum, pyknotic nuclei, and cellular fragmentation. mTOR, S6K1, and STAT3 levels were downregulated, however p53 level was modulated in PTE-treated cells. The anticancer potential of PTE might be related to its ability to alter the ultrastructure morphology, reduce mitotic activity, and modulate some key protein required for cell proliferation, suggesting its potential to trigger cancer cells towards apoptosis.
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spelling doaj.art-28d33bf3450b40669d3cafcfc3e7fd782023-08-04T05:46:14ZengElsevierSaudi Journal of Biological Sciences1319-562X2023-08-01308103717Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markersMahmoud I. Khalil0Alaa F. Agamy1Salma S. Elshewemi2Ahmed S. Sultan3Nabila E. Abdelmeguid4Department of Biological Sciences, Faculty of Science, Beirut Arab University, Lebanon; Molecular Biology Unit, Zoology Department, Faculty of Science, Alexandria University, Egypt; Corresponding author at: Department of Biological Sciences, Faculty of Science, Beirut Arab University, Lebanon. Molecular Biology Unit, Zoology Department, Faculty of Science, Alexandria University, Egypt.Molecular Biology Unit, Zoology Department, Faculty of Science, Alexandria University, EgyptZoology Department, Faculty of Science, Alexandria University, EgyptBiochemistry Department, Faculty of Science, Alexandria University, EgyptZoology Department, Faculty of Science, Alexandria University, EgyptWorldwide, hepatocellular carcinoma (HCC) is considered the sixth most prevalent cancer and ranked third in causes leading to death. Pterostilbene (PTE), a dimethylated analog of resveratrol, is a phytochemical found in fruits such as blueberries and grapes, and is known for its anticancer effect. The current study intended to investigate the effect of PTE on HepG2 cells. Cell viability, colony-forming potential, lipid peroxidation, catalase enzyme (CAT), superoxide dismutase (SOD), and caspase 3 activities, histone release, and expression levels of mTOR, S6K1, p53, and STAT3 proteins were assessed in PTE-treated HepG2 cells. In addition, the cellular and ultrastructural alterations were evaluated by light and transmission electron microscopy. PTE induced a significant reduction in HepG2 viability in a dose-dependent manner (IC50 of PTE = 74 ± 6 μM), accompanied by a decrease in colony formation potential. PTE-treated cancer cells exhibited a decrease in lipid peroxidation and CAT activity, and an increase in histone release, caspase-3, and SOD activities. Ultrastructurally, PTE-treated cells exhibited notable cell shrinkage, reduced number of filopodia, increased vacuolization, apoptotic bodies, accumulation of lipid droplets, enlarged mitochondria, dilated endoplasmic reticulum, pyknotic nuclei, and cellular fragmentation. mTOR, S6K1, and STAT3 levels were downregulated, however p53 level was modulated in PTE-treated cells. The anticancer potential of PTE might be related to its ability to alter the ultrastructure morphology, reduce mitotic activity, and modulate some key protein required for cell proliferation, suggesting its potential to trigger cancer cells towards apoptosis.http://www.sciencedirect.com/science/article/pii/S1319562X23001626PterostilbeneResveratrolHepG2ApoptosismTORP53
spellingShingle Mahmoud I. Khalil
Alaa F. Agamy
Salma S. Elshewemi
Ahmed S. Sultan
Nabila E. Abdelmeguid
Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers
Saudi Journal of Biological Sciences
Pterostilbene
Resveratrol
HepG2
Apoptosis
mTOR
P53
title Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers
title_full Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers
title_fullStr Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers
title_full_unstemmed Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers
title_short Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers
title_sort pterostilbene induces apoptosis in hepatocellular carcinoma cells biochemical pathological and molecular markers
topic Pterostilbene
Resveratrol
HepG2
Apoptosis
mTOR
P53
url http://www.sciencedirect.com/science/article/pii/S1319562X23001626
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