In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1

Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral dr...

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Main Authors: Mohammed Kaleem, Asaad Kayali, Ryan A. Sheikh, Abudukadeer Kuerban, Mohammed A. Hassan, Naif Abdullah R. Almalki, Fahad A. Al-Abbasi, Firoz Anwar, Ziad Omran, Mahmoud Alhosin
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/2/434
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author Mohammed Kaleem
Asaad Kayali
Ryan A. Sheikh
Abudukadeer Kuerban
Mohammed A. Hassan
Naif Abdullah R. Almalki
Fahad A. Al-Abbasi
Firoz Anwar
Ziad Omran
Mahmoud Alhosin
author_facet Mohammed Kaleem
Asaad Kayali
Ryan A. Sheikh
Abudukadeer Kuerban
Mohammed A. Hassan
Naif Abdullah R. Almalki
Fahad A. Al-Abbasi
Firoz Anwar
Ziad Omran
Mahmoud Alhosin
author_sort Mohammed Kaleem
collection DOAJ
description Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.
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spelling doaj.art-4b2fa2bde38a4a88be1132d9495e6b972024-01-29T14:08:35ZengMDPI AGMolecules1420-30492024-01-0129243410.3390/molecules29020434In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1Mohammed Kaleem0Asaad Kayali1Ryan A. Sheikh2Abudukadeer Kuerban3Mohammed A. Hassan4Naif Abdullah R. Almalki5Fahad A. Al-Abbasi6Firoz Anwar7Ziad Omran8Mahmoud Alhosin9Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaKing Abdullah International Medical Research Center, King Saud Bin Abdelaziz University for Health Sciences, Jeddah 21423, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBreast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.https://www.mdpi.com/1420-3049/29/2/434breast cancerthymoquinonemetastasisepigeneticsDNMT1
spellingShingle Mohammed Kaleem
Asaad Kayali
Ryan A. Sheikh
Abudukadeer Kuerban
Mohammed A. Hassan
Naif Abdullah R. Almalki
Fahad A. Al-Abbasi
Firoz Anwar
Ziad Omran
Mahmoud Alhosin
In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1
Molecules
breast cancer
thymoquinone
metastasis
epigenetics
DNMT1
title In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1
title_full In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1
title_fullStr In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1
title_full_unstemmed In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1
title_short In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1
title_sort in vitro and in vivo preventive effects of thymoquinone against breast cancer role of dnmt1
topic breast cancer
thymoquinone
metastasis
epigenetics
DNMT1
url https://www.mdpi.com/1420-3049/29/2/434
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