The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome
High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supportin...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/7/1066 |
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| author | Rebeca Kelly Diego Aviles Catriona Krisulevicz Krystal Hunter Lauren Krill David Warshal Olga Ostrovsky |
| author_facet | Rebeca Kelly Diego Aviles Catriona Krisulevicz Krystal Hunter Lauren Krill David Warshal Olga Ostrovsky |
| author_sort | Rebeca Kelly |
| collection | DOAJ |
| description | High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in suppressing the growth of 3D ovarian cancer spheroids or organoids as well as post-treatment cancer recovery through proliferation, migration, invasion, and colony formation assays when compared to the synthetic epigenetic compound Panobinostat with or without standard chemotherapy. Finally, given the regulatory role of the secretome in growth, metastasis, chemoresistance, and relapse of disease, we demonstrate that natural epigenetic compounds can regulate the secretion of protumorigenic growth factors, cytokines, extracellular matrix components, and immunoregulatory markers in human ovarian cancer specimens. While further studies are needed, our results suggest that these treatments could be considered in the future as adjuncts to standard chemotherapy, improving efficiency and patient outcomes. |
| first_indexed | 2024-03-11T01:16:00Z |
| format | Article |
| id | doaj.art-d2d33ea1692c439599cf65d95bbc21c1 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T01:16:00Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d2d33ea1692c439599cf65d95bbc21c12023-11-18T18:30:56ZengMDPI AGBiomolecules2218-273X2023-07-01137106610.3390/biom13071066The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer SecretomeRebeca Kelly0Diego Aviles1Catriona Krisulevicz2Krystal Hunter3Lauren Krill4David Warshal5Olga Ostrovsky6Department of Gynecologic Oncology, MD Anderson Cancer Center at Cooper University Hospital, Camden, NJ 08103, USADepartment of Gynecologic Oncology, MD Anderson Cancer Center at Cooper University Hospital, Camden, NJ 08103, USACooper Medical School of Rowan University, Camden, NJ 08103, USACooper Medical School of Rowan University, Camden, NJ 08103, USADepartment of Gynecologic Oncology, MD Anderson Cancer Center at Cooper University Hospital, Camden, NJ 08103, USADepartment of Gynecologic Oncology, MD Anderson Cancer Center at Cooper University Hospital, Camden, NJ 08103, USACooper Medical School of Rowan University, Camden, NJ 08103, USAHigh mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in suppressing the growth of 3D ovarian cancer spheroids or organoids as well as post-treatment cancer recovery through proliferation, migration, invasion, and colony formation assays when compared to the synthetic epigenetic compound Panobinostat with or without standard chemotherapy. Finally, given the regulatory role of the secretome in growth, metastasis, chemoresistance, and relapse of disease, we demonstrate that natural epigenetic compounds can regulate the secretion of protumorigenic growth factors, cytokines, extracellular matrix components, and immunoregulatory markers in human ovarian cancer specimens. While further studies are needed, our results suggest that these treatments could be considered in the future as adjuncts to standard chemotherapy, improving efficiency and patient outcomes.https://www.mdpi.com/2218-273X/13/7/1066natural epigenetic compoundsovarian cancersecretometumor microenvironmentorganoidsspheroids |
| spellingShingle | Rebeca Kelly Diego Aviles Catriona Krisulevicz Krystal Hunter Lauren Krill David Warshal Olga Ostrovsky The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome Biomolecules natural epigenetic compounds ovarian cancer secretome tumor microenvironment organoids spheroids |
| title | The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome |
| title_full | The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome |
| title_fullStr | The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome |
| title_full_unstemmed | The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome |
| title_short | The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome |
| title_sort | effects of natural epigenetic therapies in 3d ovarian cancer and patient derived tumor explants new avenues in regulating the cancer secretome |
| topic | natural epigenetic compounds ovarian cancer secretome tumor microenvironment organoids spheroids |
| url | https://www.mdpi.com/2218-273X/13/7/1066 |
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