Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells
Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. <i>N</i>-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unst...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/10/2394 |
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| author | Kai-Fu Chang Jinghua Tsai Chang Xiao-Fan Huang Yu-Ling Lin Kuang-Wen Liao Chien-Wei Huang Nu-Man Tsai |
| author_facet | Kai-Fu Chang Jinghua Tsai Chang Xiao-Fan Huang Yu-Ling Lin Kuang-Wen Liao Chien-Wei Huang Nu-Man Tsai |
| author_sort | Kai-Fu Chang |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. <i>N</i>-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G<sub>0</sub>/G<sub>1</sub> and subG<sub>1</sub> phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer. |
| first_indexed | 2024-03-10T19:40:41Z |
| format | Article |
| id | doaj.art-747dc7d8445842b5be3ca3ede2b84e1b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:40:41Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-747dc7d8445842b5be3ca3ede2b84e1b2023-11-20T01:13:48ZengMDPI AGMolecules1420-30492020-05-012510239410.3390/molecules25102394Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer CellsKai-Fu Chang0Jinghua Tsai Chang1Xiao-Fan Huang2Yu-Ling Lin3Kuang-Wen Liao4Chien-Wei Huang5Nu-Man Tsai6Institute of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanDepartment of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, TaiwanDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanDepartment of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, TaiwanColorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. <i>N</i>-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G<sub>0</sub>/G<sub>1</sub> and subG<sub>1</sub> phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer.https://www.mdpi.com/1420-3049/25/10/2394<i>N</i>-butylidenephthalideLPPC nanoparticlecolorectal cancerantitumorcytotoxicity |
| spellingShingle | Kai-Fu Chang Jinghua Tsai Chang Xiao-Fan Huang Yu-Ling Lin Kuang-Wen Liao Chien-Wei Huang Nu-Man Tsai Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells Molecules <i>N</i>-butylidenephthalide LPPC nanoparticle colorectal cancer antitumor cytotoxicity |
| title | Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells |
| title_full | Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells |
| title_fullStr | Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells |
| title_full_unstemmed | Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells |
| title_short | Antitumor Effects of <i>N</i>-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells |
| title_sort | antitumor effects of i n i butylidenephthalide encapsulated in lipopolyplexs in colorectal cancer cells |
| topic | <i>N</i>-butylidenephthalide LPPC nanoparticle colorectal cancer antitumor cytotoxicity |
| url | https://www.mdpi.com/1420-3049/25/10/2394 |
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