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Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells

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Abstract

Purpose

The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells.

Methods

MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting.

Results

The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h.

Conclusions

LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future.

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Acknowledgements

Authors would like to acknowledge Instrument Center of Chung Shan Medical University for ZEISS Axio Imager A2 microscopy. The research Grants CSH-2014-C-031 and CSH-2014-A-023 from Chung Shan Medical University Hospital.

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Author notes

  1. M.-C. Hsieh and N.-M. Tsai contributed equally to this work.

Authors and Affiliations

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

    X.-F. Huang, K.-F. Chang & G.-T. Sheu

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

    X.-F. Huang, M.-S. Lee, K.-F. Chang, M.-C. Hsieh & N.-M. Tsai

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

    P.-T. Chen, M.-S. Lee, M.-C. Hsieh & N.-M. Tsai

  4. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 11529, Taiwan, ROC

    Y.-L. Lin

  5. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 30010, Taiwan, ROC

    K.-W. Liao

  6. Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 30010, Taiwan, ROC

    K.-W. Liao

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Huang, XF., Chen, PT., Lin, YL. et al. Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells. Clin Transl Oncol 23, 1142–1151 (2021). https://doi.org/10.1007/s12094-020-02500-w

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