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Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis

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Abstract

This study investigated the anti-leukemic effects of Cedrus atlantica extract (CAt extract) on cell cycle distribution and apoptosis in human acute myeloid leukemia (AML) cells. AML often occurs in older adults, accounting for 60% of the cases, and is likely to be resistant to chemotherapy due to multidrug resistance, resulting in early death during cancer treatment. With the increasing focus on prevention medicine, natural plant components are being used as a major source for the development of therapeutic drugs or functional foods to cure or alleviate the disease. Cedrus species are known to have anti-inflammatory, antimicrobial, antiviral, and anticancer effects; however, the anticancer effects of CAt extract have not been elucidated. In this study, CAt extract demonstrated an inhibitory effect on human leukemia cells in a concentration-dependent manner; CAt extract induced G0/G1 phase arrest via restrained protein levels of p-Rb and cell cycle-related proteins. After CAt extract exposure, the extrinsic and intrinsic apoptotic pathways were activated through caspase-8, -9, and -3 cleavage. Additionally, CAt extract suppressed VEGF, MMP-2, and MMP-9 expression. This study demonstrated that CAt extract treatment significantly reduced cell growth, cell cycle arrest in the G0/G1 phase, and induction of apoptosis, leading to leukemia cell death.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge Instrument Center of Chung Shan Medical University for ZEISS Axio Imager A2 microscopy and BD FASCS Calibur facility.

Funding

The research Grant CSH-2014-C-031 and CSH-2016-C-025 from Chung Shan Medical University Hospital, Taiwan and the Grant Number CSMU-CYC-101-01 was funded by Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan.

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Author notes

  1. Ming-Shih Lee and Nu-Man Tsai are corresponding authors contributed equally to this work.

Authors and Affiliations

  1. Director of Traditional Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 60002, Taiwan, ROC

    Pei-Hsiu Hung

  2. College of Biotechnology and Bioresource, Da-Yeh University, Changhua, 51591, Taiwan, ROC

    Pei-Hsiu Hung

  3. Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, 40201, Taiwan, ROC

    Ming-Chang Hsieh, Xiao-Fan Huang, Kai-Fu Chang, Szu-Yin Chen, Ming-Shih Lee & Nu-Man Tsai

  4. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan, ROC

    Ming-Chang Hsieh, Ming-Shih Lee & Nu-Man Tsai

  5. Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, 40201, Taiwan, ROC

    Shan-Chih Lee

  6. Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan, ROC

    Shan-Chih Lee

  7. Institute of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan, ROC

    Xiao-Fan Huang & Kai-Fu Chang

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Hung, PH., Hsieh, MC., Lee, SC. et al. Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis. Mol Biol Rep 47, 8935–8947 (2020). https://doi.org/10.1007/s11033-020-05947-w

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  • DOI: https://doi.org/10.1007/s11033-020-05947-w

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