Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells
Background. A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers’ attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis....
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2022/1850305 |
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| author | Zohre Miri-Lavasani Shukoofeh Torabi Roya Solhi Bahareh Shokouhian Parvaneh Afsharian Zahra Heydari Abbas Piryaei Zahra Farzaneh Nikoo Hossein-khannazer Hamidreza Aboulkheyr Es Ensieh Zahmatkesh Andreas Nussler Moustapha Hassan Mustapha Najimi Massoud Vosough |
| author_facet | Zohre Miri-Lavasani Shukoofeh Torabi Roya Solhi Bahareh Shokouhian Parvaneh Afsharian Zahra Heydari Abbas Piryaei Zahra Farzaneh Nikoo Hossein-khannazer Hamidreza Aboulkheyr Es Ensieh Zahmatkesh Andreas Nussler Moustapha Hassan Mustapha Najimi Massoud Vosough |
| author_sort | Zohre Miri-Lavasani |
| collection | DOAJ |
| description | Background. A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers’ attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2′-chloro-5′-nitrobenzenesulfonyl)−2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. Results. In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. Conclusion. CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition. |
| format | Article |
| id | doaj-art-a244842833be49c5a9cee36ec7c50d94 |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-a244842833be49c5a9cee36ec7c50d942025-02-03T01:20:35ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/1850305Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma CellsZohre Miri-Lavasani0Shukoofeh Torabi1Roya Solhi2Bahareh Shokouhian3Parvaneh Afsharian4Zahra Heydari5Abbas Piryaei6Zahra Farzaneh7Nikoo Hossein-khannazer8Hamidreza Aboulkheyr Es9Ensieh Zahmatkesh10Andreas Nussler11Moustapha Hassan12Mustapha Najimi13Massoud Vosough14Department of Regenerative MedicineDepartment of Regenerative MedicineDepartment of Regenerative MedicineDepartment of Regenerative MedicineDepartment of GeneticsDepartment of Regenerative MedicineDepartment of Biology and Anatomical SciencesDepartment of Regenerative MedicineGastroenterology and Liver Diseases Research CenterSchool of Biomedical EngineeringDepartment of Regenerative MedicineSiegfried Weller Institute for Trauma ResearchExperimental Cancer MedicineLaboratory of Pediatric Hepatology and Cell TherapyDepartment of Regenerative MedicineBackground. A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers’ attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2′-chloro-5′-nitrobenzenesulfonyl)−2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. Results. In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. Conclusion. CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition.http://dx.doi.org/10.1155/2022/1850305 |
| spellingShingle | Zohre Miri-Lavasani Shukoofeh Torabi Roya Solhi Bahareh Shokouhian Parvaneh Afsharian Zahra Heydari Abbas Piryaei Zahra Farzaneh Nikoo Hossein-khannazer Hamidreza Aboulkheyr Es Ensieh Zahmatkesh Andreas Nussler Moustapha Hassan Mustapha Najimi Massoud Vosough Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells Stem Cells International |
| title | Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells |
| title_full | Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells |
| title_fullStr | Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells |
| title_short | Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells |
| title_sort | conjugated linoleic acid treatment attenuates cancerous features in hepatocellular carcinoma cells |
| url | http://dx.doi.org/10.1155/2022/1850305 |
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