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Eriodictyol inhibits breast carcinogenesis by targeting circ_0007503 and repressing PI3K/Akt pathway

Jianbo He¹, Hongjuan Fu¹, Cancan Li¹

¹College of Food Science, Southwest University, No.2 Tiansheng Road, BeiBei District, Chongqing 400715, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology

|May 17, 2022

Abstract

Background:

Eriodictyol in citrus fruits, Eriodictyon californicum and several Chinese herbal medicines shows great promise for chronic disease prevention, including cancers. However, its role in chemopreventive activities against breast carcinogenesis is unknown.

Purpose:

In the present study, we investigated the chemopreventive effect and the underlying mechanism of eriodictyol on carcinogens-induced breast carcinogenesis in vivo and in vitro.

Methods:

The carcinogenic transformation in MCF10A cells was induced by the environmental carcinogens in vitro. The chemopreventive effect in vivo was evaluated by using the experimental model of 1-methyl-1-nitrosourea (MNU)-induced mammary tumorigenesis in rats. The activation of the PI3K/Akt pathway was detected by western blot assay; the levels of circular RNAs (circRNAs) were measured by qRT-PCR.

Results:

First, eriodictyol significantly reduces cells viability and induces apoptosis in breast cancer cells in a dose-dependent manner in vitro (P < 0.05). Next, eriodictyol could effectively suppress environmental carcinogens-induced acquisition of carcinogenic properties in human breast epithelial cell MCF10A (P < 0.05). In vivo, eriodictyol administration reduces the incidence of mammary tumor by 50% in carcinogen-treated female rats (P < 0.05). Further study revealed that eriodictyol represses the PI3K/Akt signaling pathway and down-regulates the level of circ_0007503 in breast cancer cells and in breast carcinogenesis (P < 0.01). When the effect of eriodictyol on circ_0007503 was blocked by transfection of a circ_0007503 over-expression plasmid, the cytotoxic effects and the suppression of the PI3K/Akt pathway of eriodictyol in breast cancer cells were significantly reduced (P < 0.05).

Conclusion:

Our data indicated that eriodictyol could effectively suppress breast carcinogenesis in vitro and in vivoThe mechanism may be attributed to targeting circ_0007503 and inhibiting PI3K/Akt pathway.

Insights

Eriodictyol, a compound found in citrus fruits, shows significant promise in preventing breast cancer. It effectively reduces tumor incidence and growth by targeting circ_0007503 and inhibiting the PI3K/Akt pathway.

Area of Science:

Biochemistry
Molecular Biology
Oncology

Background:

Eriodictyol, found in citrus fruits and herbal medicines, demonstrates potential for chronic disease prevention, including cancer.
Its specific role in preventing breast cancer (chemoprevention) has not been previously established.

Purpose of the Study:

To investigate the chemopreventive effects of eriodictyol against breast cancer.
To elucidate the underlying molecular mechanisms of eriodictyol's action in both in vitro and in vivo models.

Main Methods:

Breast cancer cells (MCF10A) were induced using environmental carcinogens in vitro.
In vivo studies utilized a rat model of 1-methyl-1-nitrosourea (MNU)-induced mammary tumors.
Key molecular pathways, including PI3K/Akt signaling and circular RNA (circ_0007503) levels, were analyzed using Western blot and qRT-PCR.

Main Results:

Eriodictyol significantly reduced breast cancer cell viability and induced apoptosis in a dose-dependent manner.
It suppressed the acquisition of carcinogenic properties in human breast epithelial cells induced by environmental carcinogens.
In vivo, eriodictyol administration halved the incidence of mammary tumors in rats and downregulated circ_0007503 and the PI3K/Akt pathway.

Conclusions:

Eriodictyol effectively suppresses breast carcinogenesis both in vitro and in vivo.
The chemopreventive mechanism involves targeting circ_0007503 and inhibiting the PI3K/Akt signaling pathway.

Read full analysis

Keywords:

Breast cancer Carcinogenesis Eriodictyol Flavonoids circRNAs

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