Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the second and sixth leading cause of cancer death in men and woman in 185 countries statistics, respectively. n-Butylidenephthalide (BP) has shown anti-HCC activity, but it also has an unstable structure that decreases its potential antitumor activity. The aim of t...
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Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2021/8817875 |
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doaj-ced37d7ca3914d7ca0560471ed8c69e92021-03-29T00:10:20ZengHindawi LimitedBioMed Research International2314-61412021-01-01202110.1155/2021/8817875Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular CarcinomaKai-Fu Chang0Xiao-Fan Huang1Yu-Ling Lin2Kuang-Wen Liao3Ming-Chang Hsieh4Jinghua Tsai Chang5Nu-Man Tsai6Institute of MedicineInstitute of MedicineAgricultural Biotechnology Research CenterDepartment of Biological Science and TechnologyDepartment of Medical Laboratory and BiotechnologyInstitute of MedicineDepartment of Medical Laboratory and BiotechnologyHepatocellular carcinoma (HCC) is the second and sixth leading cause of cancer death in men and woman in 185 countries statistics, respectively. n-Butylidenephthalide (BP) has shown anti-HCC activity, but it also has an unstable structure that decreases its potential antitumor activity. The aim of this study was to investigate the cell uptake, activity protection, and antitumor mechanism of BP encapsulated in the novel liposome LPPC in HCC cells. BP/LPPC exhibited higher cell uptake and cytotoxicity than BP alone, and combined with clinical drug etoposide (VP-16), BP/LPPC showed a synergistic effect against HCC cells. Additionally, BP/LPPC increased cell cycle regulators (p53, p-p53, and p21) and decreased cell cycle-related proteins (Rb, p-Rb, CDK4, and cyclin D1), leading to cell cycle arrest at the G0/G1 phase in HCC cells. BP/LPPC induced cell apoptosis through activation of both the extrinsic (Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways and activated the caspase cascade to trigger HCC cell death. In conclusion, the LPPC complex improved the antitumor activity of BP in terms of cytotoxicity, cell cycle regulation and cell apoptosis, and BP/LPPC synergistically inhibited cell growth during combination treatment with VP-16 in HCC cells. Therefore, BP/LPPC is potentially a good candidate for clinical drug development or for use as an adjuvant for clinical drugs as a combination therapy for hepatocellular carcinoma.http://dx.doi.org/10.1155/2021/8817875 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kai-Fu Chang Xiao-Fan Huang Yu-Ling Lin Kuang-Wen Liao Ming-Chang Hsieh Jinghua Tsai Chang Nu-Man Tsai |
spellingShingle |
Kai-Fu Chang Xiao-Fan Huang Yu-Ling Lin Kuang-Wen Liao Ming-Chang Hsieh Jinghua Tsai Chang Nu-Man Tsai Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma BioMed Research International |
author_facet |
Kai-Fu Chang Xiao-Fan Huang Yu-Ling Lin Kuang-Wen Liao Ming-Chang Hsieh Jinghua Tsai Chang Nu-Man Tsai |
author_sort |
Kai-Fu Chang |
title |
Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma |
title_short |
Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma |
title_full |
Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma |
title_fullStr |
Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma |
title_full_unstemmed |
Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma |
title_sort |
positively charged nanoparticle delivery of n-butylidenephthalide enhances antitumor effect in hepatocellular carcinoma |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6141 |
publishDate |
2021-01-01 |
description |
Hepatocellular carcinoma (HCC) is the second and sixth leading cause of cancer death in men and woman in 185 countries statistics, respectively. n-Butylidenephthalide (BP) has shown anti-HCC activity, but it also has an unstable structure that decreases its potential antitumor activity. The aim of this study was to investigate the cell uptake, activity protection, and antitumor mechanism of BP encapsulated in the novel liposome LPPC in HCC cells. BP/LPPC exhibited higher cell uptake and cytotoxicity than BP alone, and combined with clinical drug etoposide (VP-16), BP/LPPC showed a synergistic effect against HCC cells. Additionally, BP/LPPC increased cell cycle regulators (p53, p-p53, and p21) and decreased cell cycle-related proteins (Rb, p-Rb, CDK4, and cyclin D1), leading to cell cycle arrest at the G0/G1 phase in HCC cells. BP/LPPC induced cell apoptosis through activation of both the extrinsic (Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways and activated the caspase cascade to trigger HCC cell death. In conclusion, the LPPC complex improved the antitumor activity of BP in terms of cytotoxicity, cell cycle regulation and cell apoptosis, and BP/LPPC synergistically inhibited cell growth during combination treatment with VP-16 in HCC cells. Therefore, BP/LPPC is potentially a good candidate for clinical drug development or for use as an adjuvant for clinical drugs as a combination therapy for hepatocellular carcinoma. |
url |
http://dx.doi.org/10.1155/2021/8817875 |
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