Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells
Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women’s cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeut...
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doaj-b68307ad50684ad79e8d0654fa4b53b62021-01-05T00:01:05ZengMDPI AGCancers2072-66942021-01-011313613610.3390/cancers13010136Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer CellsChing-Hsuan Liu0Shu Hui Wong1Chen-Jei Tai2Cheng-Jeng Tai3Yu-Chi Pan4Hsue-Yin Hsu5Christopher D. Richardson6Liang-Tzung Lin7Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanInternational M.Sc. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Traditional Chinese Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanDepartment of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Life Sciences, Tzu-Chi University, Hualien 970, TaiwanDepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, CanadaGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanOncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women’s cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA’s potentiation of apoptotic killing by MV. To circumvent UA’s poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA’s applicability.https://www.mdpi.com/2072-6694/13/1/136oncolytic virotherapymeasles virusursolic acidnanoparticlescombination treatment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ching-Hsuan Liu Shu Hui Wong Chen-Jei Tai Cheng-Jeng Tai Yu-Chi Pan Hsue-Yin Hsu Christopher D. Richardson Liang-Tzung Lin |
spellingShingle |
Ching-Hsuan Liu Shu Hui Wong Chen-Jei Tai Cheng-Jeng Tai Yu-Chi Pan Hsue-Yin Hsu Christopher D. Richardson Liang-Tzung Lin Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells Cancers oncolytic virotherapy measles virus ursolic acid nanoparticles combination treatment |
author_facet |
Ching-Hsuan Liu Shu Hui Wong Chen-Jei Tai Cheng-Jeng Tai Yu-Chi Pan Hsue-Yin Hsu Christopher D. Richardson Liang-Tzung Lin |
author_sort |
Ching-Hsuan Liu |
title |
Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells |
title_short |
Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells |
title_full |
Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells |
title_fullStr |
Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells |
title_full_unstemmed |
Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells |
title_sort |
ursolic acid and its nanoparticles are potentiators of oncolytic measles virotherapy against breast cancer cells |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-01-01 |
description |
Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women’s cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA’s potentiation of apoptotic killing by MV. To circumvent UA’s poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA’s applicability. |
topic |
oncolytic virotherapy measles virus ursolic acid nanoparticles combination treatment |
url |
https://www.mdpi.com/2072-6694/13/1/136 |
work_keys_str_mv |
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