Shotgun Lipidomics Elucidates the Lipidome  Alterations of the Mcl-1 Inhibitor S63845 in AML  Cell Lines with a Focus on Sphingolipids

Kartal Yandım Melis; Bilgin Mesut

doi:https://dx.doi.org/10.26650/experimed.1196117

Research Article

DOI :10.26650/experimed.1196117 IUP :10.26650/experimed.1196117 Full Text (PDF)

Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids

Objective: Acute myeloid leukemia (AML) is a vigorous type of leukemia requiring effective treatment. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic molecule that is upregulated in AML and is studied as a target for treatment. The specific Mcl-1 inhibitor, S63845, has antiproliferative effects on AML cells. Bioactive sphingolipids have crucial roles in cells and regulate Mcl-1 stability. This study aimed to elucidate the changes in lipid profiles of AML cell lines in response to Mcl-1 inhibitor S63845 treatment, with a special focus on sphingolipids. Materials and Methods: The cytotoxic effects of S63845 were identified in the AML cell lines MV4-11, HL60, and KG1 using the MTT cell proliferation assay. Lipidome analysis was conducted by quantitative shotgun lipidomics covering 378 individual lipid species in 26 classes within the major lipid categories. Results: The IC50 values of S63845 have been calculated as 7 nM for MV4-11, 53 nM for HL60, and 479 nM for KG1. The lipidome results reveal the S63845 treatment to increase ceramide (Cer) levels in the MV4-11 and KG1 cell lines at the expense of downstream sphingolipids while increasing the hexosylceramide (HexCer) levels in the HL60 cell line at the expense of the Cer and sphingomyelin (SM). Conclusion: This study showed S63845 to be able to suppress cell proliferation by altering lipid compositions in AML cell lines. More importantly, the study suggested S63845 to differentially affect the lipid profiles of AML cell lines.

Keywords: Mcl-1, small molecule inhibitors, S63845, acute myeloid leukemia, shotgun lipidomics, bioactive sphingolipids

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APA

Kartal Yandım, M., & Bilgin, M. (2022). Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids. Experimed, 12(3), 209-214. https://doi.org/10.26650/experimed.1196117

AMA

Kartal Yandım M, Bilgin M. Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids. Experimed. 2022;12(3):209-214. https://doi.org/10.26650/experimed.1196117

ABNT

Kartal Yandım, M.; Bilgin, M. Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids. Experimed, [Publisher Location], v. 12, n. 3, p. 209-214, 2022.

Chicago: Author-Date Style

Kartal Yandım, Melis, and Mesut Bilgin. 2022. “Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids.” Experimed 12, no. 3: 209-214. https://doi.org/10.26650/experimed.1196117

Chicago: Humanities Style

Kartal Yandım, Melis, and Mesut Bilgin. “Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids.” Experimed 12, no. 3 (Sep. 2024): 209-214. https://doi.org/10.26650/experimed.1196117

Harvard: Australian Style

Kartal Yandım, M & Bilgin, M 2022, 'Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids', Experimed, vol. 12, no. 3, pp. 209-214, viewed 9 Sep. 2024, https://doi.org/10.26650/experimed.1196117

Harvard: Author-Date Style

Kartal Yandım, M. and Bilgin, M. (2022) ‘Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids’, Experimed, 12(3), pp. 209-214. https://doi.org/10.26650/experimed.1196117 (9 Sep. 2024).

MLA

Kartal Yandım, Melis, and Mesut Bilgin. “Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids.” Experimed, vol. 12, no. 3, 2022, pp. 209-214. [Database Container], https://doi.org/10.26650/experimed.1196117

Vancouver

Kartal Yandım M, Bilgin M. Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids. Experimed [Internet]. 9 Sep. 2024 [cited 9 Sep. 2024];12(3):209-214. Available from: https://doi.org/10.26650/experimed.1196117 doi: 10.26650/experimed.1196117

ISNAD

Kartal Yandım, Melis - Bilgin, Mesut. “Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in AML Cell Lines with a Focus on Sphingolipids”. Experimed 12/3 (Sep. 2024): 209-214. https://doi.org/10.26650/experimed.1196117

Volume 12, Issue 32022, P. 209-214

TIMELINE

Submitted	30.10.2022
Accepted	05.12.2022
Published Online	30.12.2022

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