Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)

Accumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which pl...

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Main Authors: Izabela Szymczak-Pajor, Józef Drzewoski, Ewa Świderska, Justyna Strycharz, Anna Gabryanczyk, Jacek Kasznicki, Marta Bogdańska, Agnieszka Śliwińska
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/16/1/115
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author Izabela Szymczak-Pajor
Józef Drzewoski
Ewa Świderska
Justyna Strycharz
Anna Gabryanczyk
Jacek Kasznicki
Marta Bogdańska
Agnieszka Śliwińska
author_facet Izabela Szymczak-Pajor
Józef Drzewoski
Ewa Świderska
Justyna Strycharz
Anna Gabryanczyk
Jacek Kasznicki
Marta Bogdańska
Agnieszka Śliwińska
author_sort Izabela Szymczak-Pajor
collection DOAJ
description Accumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which plays a key role in carcinogenesis, remains unclear. Therefore, the aim of our study was to evaluate the impact of metformin on histone acetyltransferases (HATs) (i.e., p300/CBP-associated factor (PCAF), p300, and CBP) and on histone deacetylases (HDACs) (i.e., SIRT-1 in human pancreatic cancer (PC) cell lines, 1.2B4, and PANC-1). The cells were exposed to metformin, an HAT inhibitor (HATi), or a combination of an HATi with metformin for 24, 48, or 72 h. Cell viability was determined using an MTT assay, and the percentage of early apoptotic cells was determined with an Annexin V-Cy3 Apoptosis Detection Assay Kit. Caspase-9 activity was also assessed. <i>SIRT-1</i>, <i>PCAF</i>, <i>p300</i>, and <i>CBP</i> expression were determined at the mRNA and protein levels using RT-PCR and Western blotting methods, respectively. Our results reveal an increase in caspase-9 in response to the metformin, indicating that it induced the apoptotic death of both 1.2B4 and PANC-1 cells. The number of cells in early apoptosis and the activity of caspase-9 decreased when treated with an HATi alone or a combination of an HATi with metformin, as compared to metformin alone. Moreover, metformin, an HATi, and a combination of an HATi with metformin also modified the mRNA expression of <i>SIRT-1</i>, <i>PCAF</i>, <i>CBP</i>, and <i>p300</i>. However, metformin did not change the expression of the studied genes in 1.2B4 cells. The results of the Western blot analysis showed that metformin diminished the protein expression of PCAF in both the 1.2B4 and PANC-1 cells. Hence, it appears possible that PCAF may be involved in the metformin-mediated apoptosis of PC cells.
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spelling doaj.art-9bb8afdd0bb543209d563f005c79013f2023-11-30T23:56:00ZengMDPI AGPharmaceuticals1424-82472023-01-0116111510.3390/ph16010115Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)Izabela Szymczak-Pajor0Józef Drzewoski1Ewa Świderska2Justyna Strycharz3Anna Gabryanczyk4Jacek Kasznicki5Marta Bogdańska6Agnieszka Śliwińska7Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandCentral Teaching Hospital of the Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, PolandDepartment of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandDepartment of Internal Diseases, Diabetology and Clinical Pharmacology, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandStudent Scientific Society of Civilization Diseases, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandDepartment of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandAccumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which plays a key role in carcinogenesis, remains unclear. Therefore, the aim of our study was to evaluate the impact of metformin on histone acetyltransferases (HATs) (i.e., p300/CBP-associated factor (PCAF), p300, and CBP) and on histone deacetylases (HDACs) (i.e., SIRT-1 in human pancreatic cancer (PC) cell lines, 1.2B4, and PANC-1). The cells were exposed to metformin, an HAT inhibitor (HATi), or a combination of an HATi with metformin for 24, 48, or 72 h. Cell viability was determined using an MTT assay, and the percentage of early apoptotic cells was determined with an Annexin V-Cy3 Apoptosis Detection Assay Kit. Caspase-9 activity was also assessed. <i>SIRT-1</i>, <i>PCAF</i>, <i>p300</i>, and <i>CBP</i> expression were determined at the mRNA and protein levels using RT-PCR and Western blotting methods, respectively. Our results reveal an increase in caspase-9 in response to the metformin, indicating that it induced the apoptotic death of both 1.2B4 and PANC-1 cells. The number of cells in early apoptosis and the activity of caspase-9 decreased when treated with an HATi alone or a combination of an HATi with metformin, as compared to metformin alone. Moreover, metformin, an HATi, and a combination of an HATi with metformin also modified the mRNA expression of <i>SIRT-1</i>, <i>PCAF</i>, <i>CBP</i>, and <i>p300</i>. However, metformin did not change the expression of the studied genes in 1.2B4 cells. The results of the Western blot analysis showed that metformin diminished the protein expression of PCAF in both the 1.2B4 and PANC-1 cells. Hence, it appears possible that PCAF may be involved in the metformin-mediated apoptosis of PC cells.https://www.mdpi.com/1424-8247/16/1/115metforminpancreatic cancer (PC)histone acetyltransferases (HATs)histone deacetylases (HDACs)
spellingShingle Izabela Szymczak-Pajor
Józef Drzewoski
Ewa Świderska
Justyna Strycharz
Anna Gabryanczyk
Jacek Kasznicki
Marta Bogdańska
Agnieszka Śliwińska
Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)
Pharmaceuticals
metformin
pancreatic cancer (PC)
histone acetyltransferases (HATs)
histone deacetylases (HDACs)
title Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)
title_full Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)
title_fullStr Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)
title_full_unstemmed Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)
title_short Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels)
title_sort metformin induces apoptosis in human pancreatic cancer pc cells accompanied by changes in the levels of histone acetyltransferases particularly p300 cbp associated factor pcaf protein levels
topic metformin
pancreatic cancer (PC)
histone acetyltransferases (HATs)
histone deacetylases (HDACs)
url https://www.mdpi.com/1424-8247/16/1/115
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