Effect of dietary flavonols on oestrogen receptor transactivation and cell death induction

Abstract

Consumption of fruits and vegetables has been associated with cancer prevention; flavonoids are widely distributed in plant foods and considered to be the active ingredients. Quercetin and kaempferol are two of the most commonly found dietary flavonols, and have been reported to prevent cancer. We have previously reported that the isoflavone genistein and the flavone baicalein exert differential actions on the oestrogen receptor (OR) a in HepG2 cells. Because of the structural resemblance to both isoflavone and flavone, we examined the effects of these dietary flavonols on ORa -and ORb -specific transactivations and their subsequent involvement in inducing MCF-7 cell death. In the present study, both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORa and -b expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17b-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 mM-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells. Cell death ELISA assay performed on MCF-7 cells indicated that an increase of apoptosis occurred at 25 mM-, but not 10 mM-, quercetin or kaempferol. Indirectly the results suggest that OR activation is not sufficient to induce apoptosis and that apoptosis is induced despite an increase in Bcl-2 expression.

Combining naturally occurring polyphenols with TNF-related apoptosis-inducing ligand: a promising approach to kill resistant cancer cells?

“…However, it should be noted that the membrane levels of DR5 or DR4 were not assessed in this study, so the absence of blockade after DR4 silencing could be explained by a lack of DR4 at the cell surface. Consistent with a previous study [72], Bcl-2 was surprisingly upregulated by kaempferol without compromising TRAIL-induced cell death. Association of kaempferol with TRAIL was also effective in the prostate carcinoma cell line PC-3 [71], and in three out of seven gliomas [73].…”

Microwave-Assisted Extraction of Herbacetin Diglucoside from Flax (Linum usitatissimum L.) Seed Cakes and Its Quantification using an RP-HPLC-UV System

“…Human intervention trials with isolated flavonols have demonstrated an anti-hypertensive effect. Besides their high antioxidant capacity, flavonols are also known to interact with estrogenic receptors [12]. Various studies have shown that flavonols have properties that alleviate several diseases, including inflammation and cancer [13].…”

Some New Routes for the Preparation of 3-Amino-2-phenyl-4(1H)-quinolinones from Anthranilamides

“…The cyclization of esters of anthranilic acids and 2-hydroxyketones has been studied for some time. Originally, the formation of a seven-membered ring was described in the literature. , It was proved later that rearrangement to a six-membered ring takes place leading to a general, simple, and efficient synthetic entry into 2-substituted-3-hydroxy-4(1 H )-quinolinones. − These compounds are interesting because they can be considered as isosteres of flavonols, which are well-known for their applications in medicine 6 and for the various kinds of biological activity they exhibit . For this reason, and in an effort to improve the synthesis, the course of the cyclization of anthranilamides 2 under various conditions was studied.…”

“…[3][4][5] These compounds are interesting because they can be considered as isosteres of flavonols, which are well-known for their applications in medicine 6 and for the various kinds of biological activity they exhibit. 7 For this reason, and in an effort to improve the synthesis, the course of the cyclization of anthranilamides 2 under various conditions was studied. Scheme 1 outlines the reaction conditions and final products.…”