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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Periplaneta Americana Extract CII-3 (PAE CII-3) Triggers the Aging of K562 Cells by Modulating SIRT1/TSC2/mTOR Molecules

Author(s): Ziyun Tang, Xuan Wang, Si-Yue He, Yue Zhou*, Chenggui Zhang*, Heng Liu, Ziying Bi and Minrui Li

Volume 21, Issue 14, 2024

Published on: 19 October, 2023

Page: [2990 - 2997] Pages: 8

DOI: 10.2174/0115701808252949231012113909

Price: $65

Abstract

Background: Chronic myeloid leukemia (CML) is considered a type of hematopoietic stem cell disease that affects the bone marrow and blood.

Objective: This study aimed to investigate the possible role of the Periplaneta americana extract CII-3 (PAE CII-3) in the aging of K562 cells.

Materials and Methods: The proliferation and cell cycle of K562 cells were determined using the CCK-8 assay and the cell cycle assay, respectively. K562 cells were stained with SA-β-Gal to evaluate cell aging. The mitochondrial membrane potential of K562 cells was detected with the JC-1 mitochondrial membrane potential assay kit. Telomerase activity was verified using the PCR assay. The transcription of silencing information regulator 2 related enzyme 1 (SIRT1), TSC2, and the mTOR gene were evaluated with RT-PCR assay. The expression of SIRT1, p-TSC2, and p-mTOR was examined using a Western blot assay.

Results: PAE CII-3 at all concentrations (5, 10, 20, 40, 80, 160 μg/mL) demonstrated obvious inhibitory effects on K562 cell proliferation, among which 80 μg/mL showed the highest inhibitory effect. PAE CII-3 significantly blocked the cell cycle and reduced the colony-forming unit (CFU) of K562 cells compared to those in the Control group (p < 0.001). PAE CII-3 markedly increased positive SA-β-Gal staining K562 cells compared to the Control group (p < 0.001). PAE CII-3 significantly reduced mitochondrial membrane potential and decreased TERT gene transcription in K562 cells compared to those of the Control group (p < 0.001). The transcription of the SIRT1 gene (p < 0.01) and the TCS2 gene (p < 0.001) was markedly decreased, and the transcription of the mTOR gene (p < 0.05) was significantly increased in K562 cells treated with PAE CII-3 compared to those of the Control group. PAE CII-3 significantly decreased the expression of SIRT1 (p < 0.01) and p-TSC2 (p < 0.001) and upregulated the expression of p-mTOR (p < 0.01) in K562 cells compared to those of the Control group.

Conclusion: PAE CII-3 treatment could trigger aging in K562 cells by activating the SIRT1/TSC2/mTOR signaling pathway. This study would provide a potential hypothesis of the mechanism by which PAE CII-3 treatment induces the aging of chronic myeloid leukemia cells.

Keywords: Chronic myeloid leukemia (CML), Periplaneta americana extract CII-3 (PAE CII-3), aging, traditional Chinese medicine, apoptosis, hematopoietic stem cell.

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