Apigenin Inhibits Growth of Breast Cancer Cells: The Role of ERα and HER2/neu

Abstract

Phytoestrogens are a group of plant-derived compounds with an estrogen-like activity. In mammalians, phytoestrogens bind to the estrogen receptor (ER) and participate in the regulation of cell growth and gene transcription. There are several reports of the cytotoxic effects of phytoestrogens in different cancer cell lines. The aim of this study was to measure the phytoestrogen activity against breast cancer cells with different levels of ER expression and to elucidate the molecular pathways regulated by the leader compound. Methods used in the study include immunoblotting, transfection with a luciferase reporter vector, and a MTT test. We demonstrated the absence of a significant difference between ER+ and ER– breast cancer cell lines in their response to cytotoxic stimuli: treatment with high doses of phytoestrogens (apigenin, genistein, quercetin, naringenin) had the same efficiency in ER-positive and ER-negative cells. Incubation of breast cancer cells with apigenin revealed the highest cytotoxicity of this compound; on the contrary, naringenin treatment resulted in a low cytotoxic activity. It was shown that high doses of apigenin (50 μM) do not display estrogen-like activity and can suppress ER activation by 17β-estradiol. Cultivation of HER2-positive breast cancer SKBR3 cells in the presence of apigenin resulted in a decrease in HER2/neu expression, accompanied by cleavage of an apoptosis substrate PARP. Therefore, the cytotoxic effects of phytoestrogens are not associated with the steroid receptors of breast cancer cells. Apigenin was found to be the most effective phytoestrogen that strongly inhibits the growth of breast cancer cells, including HER2-positive ones.

Apoptosis Induced by (−)-Epicatechin in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species

“…For this reason, we propose that (−)-epicatechin could be acted by a different mechanism. Although the effects of (−)-epicatechin on ER-positive and ER-negative breast cancer cells are consistent with observations with other flavonoids [35][36][37], the cellular targets remain unknown.…”

Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma

“…We suppose that the additive and synergistic activities of various phenolics present in CLOs were responsible for distinct tumour‐suppressive effects against rat mammary carcinogenesis in this study. Despite the fact that single phytochemicals demonstrated significant antioxidant and anticancer effects in several studies using different cancer cell lines , we have found that resveratrol administered alone did not indicate any anticancer effects in two repeated studies (with different doses and a way of administration) using the same model of mammary carcinogenesis in rats . It is questionable whether an isolated plant secondary metabolite has the similar anticancer activities as the whole‐plant‐based food containing the cocktail of phytochemicals .…”

Apigenin inhibits NF-κB and Snail signaling, EMT and metastasis in human hepatocellular carcinoma

“…Apigenin has anti-metastatic activity and low cytotoxicity in various cancer cells, but the details of the mechanisms underlying this effect remain unclear [10–12]. Our results show that treatment with apigenin at concentrations ranging from 25–50% of the IC50 value inhibits migration and invasion in HCC cell lines.…”