Fermentation Extract of Naringenin Increases the Expression of Estrogenic Receptor β and Modulates Genes Related to the p53 Signalling Pathway, miR-200c and miR-141 in Human Colon Cancer Cells Exposed to BPA

Abstract

The estrogenic receptor beta (ERβ) protects against carcinogenesis by stimulating apoptosis. Bisphenol A (BPA) is related to promoting cancer, and naringenin has chemoprotective activities both can bind to ERβ. Naringenin in the colon is metabolized by the microbiota. Cancer involves genetic and epigenetic mechanisms, including miRNAs. The objective of the present study was to evaluate the co-exposure effect of colonic in vitro fermented extract of naringenin (FEN) and BPA, to elucidate molecular effects in HT-29 colon cancer cell line. For this, we quantified genes related to the p53 signaling pathway as well as ERβ, miR-200c, and miR-141. As an important result, naringenin (IC50 250 µM) and FEN (IC50 37%) promoted intrinsic pathways of apoptosis through phosphatase and tensin homolog (PTEN) (+2.70, +1.72-fold, respectively) and CASP9 (+3.99, +2.03-fold, respectively) expression. BPA decreased the expression of PTEN (−3.46-fold) gene regulated by miR-200. We suggest that once co-exposed, cells undergo a greater stress forcing them to mediate other extrinsic apoptosis mechanisms associated with death domain FASL. In turn, these findings are related to the increase of ERβ (5.3-fold with naringenin and 13.67-fold with FEN) gene expression, important in the inhibition of carcinogenic development.

A narrative review on therapeutic potential of naringenin in colorectal cancer: Focusing on molecular and biochemical processes

“…These findings collectively suggest that NAR and its fermented extract have the potential to modulate cell invasion and inhibit metastasis in colon cancer cells. 36 The results suggest NAR could act as a potential new treatment for managing colon cancer and CRC.…”

“…These compounds exert their effects through various mechanisms including the activation of estrogen receptors (ER) and the inhibition of cell proliferation. [36][37][38] NAR derivatives are produced by modifying the structure of NAR, typically by adding or substituting different functional groups at specific positions on the molecule. 39 The bulky substituents such as thiophenecarboxylate, methylbenzoate, isobutyrate, allyloxy, and phenyl carbonate are attached to position 7 of the NAR derivatives.…”

“…These by-products exhibit antioxidative and anti-inflammatory characteristics. 36,65 Bisphenol A (BPA) is a commonly used chemical in the production of polycarbonate polymers and epoxy resins. It is frequently present in food and beverage packaging, such as plastic bottles and canned foods, as well as in other consumer products, such as thermal paper receipts and dental sealants.…”

“…These genes play a crucial role in apoptosis and the control of the cell cycle. 36 ATF3 is a member of the ATF/CREB family of transcription factors. It is activated by various physiological and pathological stimuli and plays a crucial role in gene regulation.…”

“…Studies indicate that NAR can induce apoptosis and inhibit cell proliferation in human colon cancer cells. 36,125 In drug-resistant scenarios, NAR has been observed to promote intrinsic pathways of apoptosis through the expression of genes like phosphatase, PTEN, and caspase 9, indicating its ability to induce cell death in colon cancer cells. 36 Additionally, NAR, when combined with other compounds like diosmin, has been shown to enhance apoptosis in colon cancer cells, indicating its efficacy in promoting cell death in the tumor microenvironment.…”