Abstract
Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. N-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 G0/G1 and subG1 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.
Highlights
Angelica sinensis root (Danggui) is one of the most commonly used herbs in traditionalChinese medicine (TCM), and is consumed a dietary supplement in Europe and North America [1].Molecules 2020, 25, 2394; doi:10.3390/molecules25102394 www.mdpi.com/journal/moleculesN-Butylidenephthalide (BP) is the active component of Angelica sinensis; it has a molecular weight of188.23 g/mol
We aimed to investigate the protective effect of liposomal polyethylenimine and polyethylene glycol complex (LPPC) on BP activity and the antitumor effects of BP encapsulated in LPPC in colorectal cancer
The LPPC encapsulation increased the cytotoxicity of BP and selectivity toward Colorectal cancer (CRC) cells
Summary
Angelica sinensis root (Danggui) is one of the most commonly used herbs in traditionalChinese medicine (TCM), and is consumed a dietary supplement in Europe and North America [1].Molecules 2020, 25, 2394; doi:10.3390/molecules25102394 www.mdpi.com/journal/moleculesN-Butylidenephthalide (BP) is the active component of Angelica sinensis; it has a molecular weight of188.23 g/mol. Angelica sinensis root (Danggui) is one of the most commonly used herbs in traditional. N-Butylidenephthalide (BP) is the active component of Angelica sinensis; it has a molecular weight of. In terms of the antitumor effects, BP inhibits the growth of different types of cancer, such as colon cancer, brain tumor, hepatoma, and lung cancer [5,6,7,8]. BP induces p53-dependent and -independent apoptosis, regulates the levels of cyclin kinase inhibitors such as p21 and p27, and inhibits the ERK1/2 pathway to prevent tumor growth [6,8]. The structure of BP is hydrated or oxidized after dissolution in solution, which may affect the antitumor activity of BP [9,10,11,12]. The activity of BP must be preserved prior to its use in cancer therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
