Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model
Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T...
Principais autores: | , , , , , , , , |
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Formato: | Artigo |
Idioma: | English |
Publicado em: |
Multidisciplinary Digital Publishing Institute
2020
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Acesso em linha: | http://psasir.upm.edu.my/id/eprint/87714/1/ABSTRACT.pdf |
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author | Nordin, Noraini Yeap, Swee Keong Rahman, Heshu Sulaiman Zamberi, Nur Rizi Mohamad, Nurul Elyani Abu, Nadiah Masarudin, Mas Jaffri Abdullah, Rasedee Alitheen, Noorjahan Banu |
author_facet | Nordin, Noraini Yeap, Swee Keong Rahman, Heshu Sulaiman Zamberi, Nur Rizi Mohamad, Nurul Elyani Abu, Nadiah Masarudin, Mas Jaffri Abdullah, Rasedee Alitheen, Noorjahan Banu |
author_sort | Nordin, Noraini |
collection | UPM |
description | Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer. |
first_indexed | 2024-03-06T10:44:06Z |
format | Article |
id | upm.eprints-87714 |
institution | Universiti Putra Malaysia |
language | English |
last_indexed | 2024-03-06T10:44:06Z |
publishDate | 2020 |
publisher | Multidisciplinary Digital Publishing Institute |
record_format | dspace |
spelling | upm.eprints-877142022-07-06T02:58:32Z http://psasir.upm.edu.my/id/eprint/87714/ Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model Nordin, Noraini Yeap, Swee Keong Rahman, Heshu Sulaiman Zamberi, Nur Rizi Mohamad, Nurul Elyani Abu, Nadiah Masarudin, Mas Jaffri Abdullah, Rasedee Alitheen, Noorjahan Banu Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer. Multidisciplinary Digital Publishing Institute 2020 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/87714/1/ABSTRACT.pdf Nordin, Noraini and Yeap, Swee Keong and Rahman, Heshu Sulaiman and Zamberi, Nur Rizi and Mohamad, Nurul Elyani and Abu, Nadiah and Masarudin, Mas Jaffri and Abdullah, Rasedee and Alitheen, Noorjahan Banu (2020) Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model. Molecules, 25 (11). 2670 - 2680. ISSN 1420-3049 https://www.mdpi.com/1420-3049/25/11/2670 10.3390/molecules25112670 |
spellingShingle | Nordin, Noraini Yeap, Swee Keong Rahman, Heshu Sulaiman Zamberi, Nur Rizi Mohamad, Nurul Elyani Abu, Nadiah Masarudin, Mas Jaffri Abdullah, Rasedee Alitheen, Noorjahan Banu Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model |
title | Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model |
title_full | Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model |
title_fullStr | Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model |
title_full_unstemmed | Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model |
title_short | Antitumor and anti-metastatic effects of citral loaded nanostructured lipid carrier in 4T1 induced breast cancer mouse model |
title_sort | antitumor and anti metastatic effects of citral loaded nanostructured lipid carrier in 4t1 induced breast cancer mouse model |
url | http://psasir.upm.edu.my/id/eprint/87714/1/ABSTRACT.pdf |
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