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Molecules 2018, 23(12), 3224; https://doi.org/10.3390/molecules23123224

Antitumor Effect of n-Butylidenephthalide Encapsulated on B16/F10 Melanoma Cells In Vitro with a Polycationic Liposome Containing PEI and Polyethylene Glycol Complex

1
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
2
Institute of Medicine of Chung Shun Medical University, Taichung, Taiwan
3
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
4
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
5
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
6
Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
7
Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan
8
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan
*
Author to whom correspondence should be addressed.
Received: 10 November 2018 / Revised: 1 December 2018 / Accepted: 5 December 2018 / Published: 6 December 2018
(This article belongs to the Section Medicinal Chemistry)
PDF [1940 KB, uploaded 6 December 2018]

Abstract

Advanced melanoma can metastasize to distal organs from the skin and yield an aggressive disease and poor prognosis even after treatment with chemotherapeutic agents. The compound n-Butylidenephthalide (BP) is isolated from Angelica sinensis, which is used to treat anemia and gynecological dysfunction in traditional Chinese medicine. Studies have indicated that BP can inhibit cancers, including brain, lung, prostate, liver, and colon cancers. However, because BP is a natural hydrophobic compound, it is quickly metabolized by the liver within 24 h, and thus has limited potential for development in cancer therapy. This study investigated the anticancer mechanisms of BP through encapsulation with a novel polycationic liposome containing polyethylenimine (PEI) and polyethylene glycol complex (LPPC) in melanoma cells. The results demonstrated that BP/LPPC had higher cytotoxicity than BP alone and induced cell cycle arrest at the G0/G1 phase in B16/F10 melanoma cells. The BP/LPPC-treated cell indicated an increase in subG1 percentage and TUNEL positive apoptotic morphology through induction of extrinsic and intrinsic apoptosis pathways. The combination of BP and LPPC and clinical drug 5-Fluorouracil had a greater synergistic inhibition effect than did a single drug. Moreover, LPPC encapsulation improved the uptake of BP values through enhancement of cell endocytosis and maintained BP cytotoxicity activity within 24 h. In conclusion, BP/LPPC can inhibit growth of melanoma cells and induce cell arrest and apoptosis, indicating that BP/LPPC has great potential for development of melanoma therapy agents.
Keywords: melanoma; polycationic liposome containing PEI and polyethylene glycol complex (LPPC); n-Butylidenephthalide melanoma; polycationic liposome containing PEI and polyethylene glycol complex (LPPC); n-Butylidenephthalide
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Gao, H.-W.; Chang, K.-F.; Huang, X.-F.; Lin, Y.-L.; Weng, J.-C.; Liao, K.-W.; Tsai, N.-M. Antitumor Effect of n-Butylidenephthalide Encapsulated on B16/F10 Melanoma Cells In Vitro with a Polycationic Liposome Containing PEI and Polyethylene Glycol Complex. Molecules 2018, 23, 3224.

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