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A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs
Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the developme...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372966/ https://www.ncbi.nlm.nih.gov/pubmed/28335466 http://dx.doi.org/10.3390/nu9030303 |
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author | Roomi, Mohd Waheed Kalinovsky, Tatiana Rath, Matthias Niedzwiecki, Aleksandra |
author_facet | Roomi, Mohd Waheed Kalinovsky, Tatiana Rath, Matthias Niedzwiecki, Aleksandra |
author_sort | Roomi, Mohd Waheed |
collection | PubMed |
description | Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2 × 10(6) cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H & E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250 μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation with EPQ, and H & E staining showed no morphological changes below 500 μg/mL EPQ. These results suggest that EPQ has therapeutic potential in the treatment of ovarian cancer by significantly suppressing ovarian tumor incidence and growth and lung metastasis, and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells. |
format | Online Article Text |
id | pubmed-5372966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-53729662017-04-05 A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs Roomi, Mohd Waheed Kalinovsky, Tatiana Rath, Matthias Niedzwiecki, Aleksandra Nutrients Article Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2 × 10(6) cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H & E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250 μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation with EPQ, and H & E staining showed no morphological changes below 500 μg/mL EPQ. These results suggest that EPQ has therapeutic potential in the treatment of ovarian cancer by significantly suppressing ovarian tumor incidence and growth and lung metastasis, and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells. MDPI 2017-03-18 /pmc/articles/PMC5372966/ /pubmed/28335466 http://dx.doi.org/10.3390/nu9030303 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Roomi, Mohd Waheed Kalinovsky, Tatiana Rath, Matthias Niedzwiecki, Aleksandra A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs |
title | A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs |
title_full | A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs |
title_fullStr | A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs |
title_full_unstemmed | A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs |
title_short | A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs |
title_sort | specific mixture of nutrients suppresses ovarian cancer a-2780 tumor incidence, growth, and metastasis to lungs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372966/ https://www.ncbi.nlm.nih.gov/pubmed/28335466 http://dx.doi.org/10.3390/nu9030303 |
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