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A novel α,β-unsaturated ketone inhibits leukemia cell growth as PARP1 inhibitor

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Abstract

Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.

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Data availability

All the data used in this manuscript are available on request.

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Acknowledgements

Figure 5H is created with figdraw.com (https://www.figdraw.com/).

Funding

The work was supported by the Department of Science and Technology of Guizhou Province (No.QKHZC[2021]YB450, and QKHZC[2022]YB189, QKHZC[2020]4Y161, QKHZC[2024]YB068), the Guizhou Provincial Committee Organization Department (No. QKHPTRC-GCC[2022]034-1), the Science and Social Development of Anshun City (ASKS(2021)19).

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Authors and Affiliations

  1. Key Laboratory of Human Brain Bank for Functions and Diseases of Department of Education of Guizhou Province, College of Basic Medical, Guizhou Medical University, Guiyang, 550025, China

    Weijia Zhao, Min Mo, Zhiqiong Luo, Heng Luo & Baofei Sun

  2. State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China

    Weijia Zhao, Min Mo, Jia Yu, Sha Cheng, Zhiqiong Luo & Heng Luo

  3. Guizhou Provincial Engineering Research Center for Natural Drugs, Guiyang, 550014, China

    Jia Yu, Sha Cheng & Heng Luo

  4. Department of Pharmacy, An Shun City People’s Hospital, Anshun, 561000, China

    Wei Liang & Chen Yan

  5. GuiZhou KingMed Center for Clinical Laboratory Co., Ltd, Guiyang, 550014, China

    Gui** Long

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  1. Weijia Zhao
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  2. Min Mo
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  8. Chen Yan
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  9. Heng Luo
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  10. Baofei Sun
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Contributions

Data collection: WZ and MM; data analysis: WZ, JY, and SC; experimental design: CY, HL, and BS; project design: WL, GL, and ZL; data interpretation and manuscript writing: WZ; manuscript editing: JY and GL.

Corresponding authors

Correspondence to Chen Yan, Heng Luo or Baofei Sun.

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Zhao, W., Mo, M., Yu, J. et al. A novel α,β-unsaturated ketone inhibits leukemia cell growth as PARP1 inhibitor. Med Oncol 41, 113 (2024). https://doi.org/10.1007/s12032-024-02324-6

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