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Adjuvant Epigenetic Therapy of Decitabine and Suberoylanilide Hydroxamic Acid Exerts Anti-Neoplastic Effects in Acute Myeloid Leukemia Cells

1
Department of Biological Sciences, Faculty of Science, Beirut Arab University, Debbieh 5664, Lebanon
2
Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut 1102-2801, Lebanon
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1480; https://doi.org/10.3390/cells8121480
Received: 18 October 2019 / Revised: 10 November 2019 / Accepted: 18 November 2019 / Published: 21 November 2019
(This article belongs to the Special Issue Navigating Through the Epigenetic Pathways of Cancer)
Atypical epigenetic processes including histone acetylation and DNA methylation have been identified as a fundamental theme in hematologic malignancies. Such mechanisms modify gene expression and prompt, in part at least, the initiation and progression of several malignancies including acute myeloid leukemia. In the current study we determined the effects of treating KG-1 and U937 acute myeloid leukemia (AML) cells, in vitro, with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), or with a DNMT inhibitor, decitabine (DAC), or their combination, on cell proliferation, cell cycle progression, apoptosis, and expression of apoptosis-related proteins. Each of SAHA and DAC attenuated cell proliferation and induced cell cycle arrest and apoptotic cell death of KG-1 and U937 cell lines. Besides, their sequential combination improved the obtained anti-neoplastic effect: significant augmentation of growth inhibition and apoptosis induction as compared to cells treated with either drug alone. This effect was featured by the upregulated expression of Bax, cytochrome c1, p21, and cleaved caspases 8, 9, and 3, signifying the activation of both the intrinsic and extrinsic pathways of apoptosis. The sequential combination of SAHA and DAC causes a profound antitumorigenic effect in AML cell lines by inducing the expression of tumor suppressor genes. View Full-Text
Keywords: epigenetics; acute myeloid leukemia; decitabine; suberoylanilide hydroxamic acid epigenetics; acute myeloid leukemia; decitabine; suberoylanilide hydroxamic acid
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MDPI and ACS Style

Abou Najem, S.; Khawaja, G.; Hodroj, M.H.; Babikian, P.; Rizk, S. Adjuvant Epigenetic Therapy of Decitabine and Suberoylanilide Hydroxamic Acid Exerts Anti-Neoplastic Effects in Acute Myeloid Leukemia Cells. Cells 2019, 8, 1480. https://doi.org/10.3390/cells8121480

AMA Style

Abou Najem S, Khawaja G, Hodroj MH, Babikian P, Rizk S. Adjuvant Epigenetic Therapy of Decitabine and Suberoylanilide Hydroxamic Acid Exerts Anti-Neoplastic Effects in Acute Myeloid Leukemia Cells. Cells. 2019; 8(12):1480. https://doi.org/10.3390/cells8121480

Chicago/Turabian Style

Abou Najem, Sonia, Ghada Khawaja, Mohammad H. Hodroj, Patil Babikian, and Sandra Rizk. 2019. "Adjuvant Epigenetic Therapy of Decitabine and Suberoylanilide Hydroxamic Acid Exerts Anti-Neoplastic Effects in Acute Myeloid Leukemia Cells" Cells 8, no. 12: 1480. https://doi.org/10.3390/cells8121480

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