The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome

Sep 24, 2026

High mortality in ovarian cancer is driven by recurrence, metastasis, and chemoresistant disease associated with genetic and epigenetic aberrations. Adipose-derived stem cells from the omentum support tumor growth and tumorigenic microenvironment by propagating epigenetic defects. Dietary epigenetic inhibitors, EGCG and I3C, suppress 3D ovarian cancer spheroid/organoid growth and post-treatment recovery compared with Panobinostat and chemotherapy. These natural compounds also modulate secretome factors involved in proliferation, metastasis, chemoresistance, and relapse, suggesting potential adjunct value for standard care.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages27

Reading Time1 h 8 min

AccessFree to download

Abstract

Introduction

Rationale: ovarian cancer mortality and treatment limits

Epigenetics, chemoresistance, and tumor microenvironment

Synthetic epigenetic compounds and toxicity concerns

biomolecules Article The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome Rebeca Kelly 1, Diego Aviles 1, Catriona Krisulevicz 2, Krystal Hunter 2,3, Lauren Krill 1, David Warshal 1 and Olga Ostrovsky 2,3, * Citation: Kelly, R.; Aviles, D.; Krisulevicz, C.; Hunter, K.; Krill, L.; Warshal, D.; Ostrovsky, O. The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome. Biomolecules 2023, 13, 1066. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/biom13071066](10.3390/biom13071066) Academic Editor: Jorge Joven Received: 4 May 2023 Revised: 26 June 2023 Accepted: 27 June 2023 Published: 1 July 2023 Copyright: © 2023 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 ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Gynecologic Oncology, MD Anderson Cancer Center at Cooper University Hospital, Camden, NJ 08103, USA; [kelly-rebeca@cooperhealth.edu](kelly-rebeca@cooperhealth.edu) (R.K.) 2 Cooper Medical School of Rowan University, Camden, NJ 08103, USA 3 Cooper Research Institute, Cooper University Healthcare, Camden, NJ 08103, USA * Correspondence: [olgaostrovskyphd@gmail.com](olgaostrovskyphd@gmail.com) Abstract: 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. Keywords: natural epigenetic compounds; ovarian cancer; secretome; tumor microenvironment; organoids; spheroids 1. Introduction Despite countless advancements in care and treatment, ovarian cancer continues to bea challenging and deadly disease. In the United States alone, 19,880 new cases of ovarian cancer were estimated to be diagnosed in 2022 . Overall, ovarian cancer ranks ﬁfth among causes of death in women, leading to more deaths than any other gynecologic cancer [1–3] . The current standard treatment comprises a combination of cytoreductive surgery, with or without platinum-based chemotherapy [3–5] . While initial management aims to provide a cure, diagnosis at advanced stages, alongside resistance and recurrence of disease, have posed challenges to the optimal management of ovarian cance

FAQs

Why are natural epigenetic therapies considered for ovarian cancer treatment?

Because ovarian cancer mortality is linked to recurrence, metastasis, and chemoresistance that involve epigenetic aberrations in addition to genetic changes.

What role do omentum adipose-derived stem cells play in ovarian cancer progression?

Omentum adipose-derived stem cells support the tumor and tumorigenic microenvironment by inducing epigenetic abnormalities and by secreting protumorigenic cytokines and growth factors that promote chemoresistance and recurrence.

Which natural compounds are evaluated and what are their observed effects?

Epigallocatechin gallate (EGCG) and Indole-3-carbinol (I3C) are evaluated; they suppress growth of 3D ovarian cancer spheroids/organoids and affect proliferation, migration, invasion, and colony formation, with secretome-related changes that may reduce protumorigenic signaling.

Sep 24, 2026

Upload by Sophia Brooks