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The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis

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Abstract

MicroRNAs (miRs) play a crucial role in the leukemogenesis and the prognosis of acute myeloid leukemia (AML). This study investigated the therapeutic effects of resveratrol, gallic acid, and piperine as natural anticancer agents on the HL-60 cell line and their roles in apoptosis. In this experimental study, quantitative analysis of miRs, including miR-17, miR-92b, miR-181a, and miR-222, were performed in 150 newly diagnosed patients with AML by real-time PCR assay. HL-60 cell viability as well as the expression of miRs, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA, were also assessed after transfection with the LNA-miRs and treatment with resveratrol, gallic acid, and piperine. The expression of miR-17 and miR-181a decreased significantly in LNA-anti-miRs. Although HL-60 cell viability decreased in LNA-anti-miR-222, miR-17, and miR-92b, blockade of miR-181a increased the cell viability. Besides, the cell viability increased merely in the piperine-treated group. Compared to untreated cells, miR-17 and miR-92b expression significantly increased in gallic acid- and resveratrol-treated cells. In HL-60 cells treated with resveratrol, gallic acid, and piperine, the expression of miR-181a was also increased significantly. The expression of BAX was also increased in resveratrol and piperine-treated groups. Compared to untreated cells, the expression of c-Kit increased significantly in the piperine-treated group; however, it decreased in the resveratrol-treated group. LNA-anti-miRs may be a promising agent for the treatment of AML. All three compounds used in this study showed anticancer effects, which can exert the desired outcome in patients with AML.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

miRs:

MicroRNAs

AML:

Acute myeloid leukemia

BCL-2:

B-Cell Lymphoma 2

MCL-1:

Myeloid-cell leukemia 1

FAB:

French-American and British

RT-PCR:

Reverse transcriptase polymerase chain reaction

APL:

Human acute promyelocytic leukemia

WBC:

White blood cells

Hb:

Hemoglobin

LDH:

Lactate dehydrogenase

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Funding

This study was financially supported by grant No. 94–01-104–11279 from the Vice-Chancellor of Research, Shiraz University of Medical Sciences, Shiraz, Iran.

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Authors and Affiliations

  1. Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mahdiyar Iravani Saadi, Fakhroddin Hosseini, Zahra Rahimian, Maryam Ahmadyan, Zahra Ghahramani, Mehdi Dehghani, Karim Yousefi, Nadiya Kheradmand, Mani Ramzi & Nastaran Fooladivanda

  2. Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Javad Moayedi

  3. Department of Internal Medicine, Jahrom University of Medical Sciences, Jahrom, Iran

    Hossain Ali Rostamipour

  4. Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran

    Zahed Karimi

  5. Hematology, Oncology and Bone Marrow Transplantation Department, Shiraz University of Medical Sciences, Shiraz, Iran

    Mehdi Dehghani & Mani Ramzi

Authors
  1. Mahdiyar Iravani Saadi
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  2. Javad Moayedi
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  3. Fakhroddin Hosseini
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  4. Hossain Ali Rostamipour
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  6. Zahra Rahimian
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Contributions

MIS, MR, ZG analyzed and interpreted the patient data. JM, FH, HAR, NK, NF gathered the data, ZK, KY, MD, MA, ZR were major contributors in writing the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mani Ramzi or Nastaran Fooladivanda.

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The authors declare that they have no competing interests.

Ethical Approval

All stages were approved by the Ethics Committee of Shiraz University of Medical Sciences (Code: IR.SUMS.MED.REC.95–01-32–13635). In this study, human participation follows the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments.

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Iravani Saadi, M., Moayedi, J., Hosseini, F. et al. The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10582-8

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