Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 – a comparative study

Abstract

Breast cancer is one of the most common causes of mortality in women. Flavonoids, among other compounds, are bioactive constituents of propolis. In this comparative study, we investigated the effects of flavonoids apigenin (API), genistein (GEN), hesperidin (HES), naringin (NAR) and quercetin (QUE) on the proliferation, apoptosis, and cell cycle of two different human cancer cells-MDA-MB-231, estrogen-negative, and MCF-7, estrogen-positive receptor breast carcinoma cells. Many cytotoxic reports of flavonoids were performed by MTT assay. However, it's reported that MTT is reduced in metabolically active cells and yields an insoluble purple formazan, which indicates that obtained cytotoxic results of flavonoids could be inconsistent. Cell viability was measured by NR, neutral red assay, while the percentage of apoptotic cells and cell cycle arrest were determined by flow cytometry and Muse cell cycle assay, respectively. The results showed a high dose-dependent effect in cell viability tests. IC 50 values were as follows (MCF-7/MDA-MB-231, for 48 h, in µM): 9.39/50.83 for HES, 25.19/88.17 for API, 40.26/333.51 for NAR, 49.49/47.50 for GEN and 95.12/130.10 for QUE. Flavonoid-induced apoptosis was dose-and time-dependent, for both cancer cell lines, though flavonoids were more active on MCF-7 cells. The flavonoids also induced cell cycle arrest in cancer cells.

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.…”

Licochalcone A Inhibits Cellular Motility by Suppressing E-cadherin and MAPK Signaling in Breast Cancer

“…Many scholars are trying to find natural products to block the invasion and metastasis of triple-negative breast cancer cells. Previous researchers have demonstrated that many natural compounds from plants have anti-cancer effects and could induce apoptosis and arrest cell cycle in breast cancer cells [10,11,12]. Apigenin and quercetin have been reported to cause apoptosis, suppress cell proliferation, and increase the generation of reactive oxygen species (ROS) in MDA-MB-231 human breast cancer cells [13,14].…”

Bioactive Compounds and Metabolites from Grapes and Red Wine in Breast Cancer Chemoprevention and Therapy

“…Kaempferol and quercetin decrease the growth of MCF-7 and MDA-MB-231 cells with micromolar concentrations. However, the MCF-7 cell line appeared to be more sensitive to quercetin than MDA-MB-231 [41][42][43][44]. The same was observed for kaempferol in an MCF-7 3-D model, with ERK signaling being responsible for the apoptotic death [45] and cell cycle arrest at the sub-G1 phase [40].…”

“…Quercetin has been widely reported for its activity against breast cancer cell lines such as MCF-7 and MDA-MB-231 [47][48][49]. The mechanisms of action involved apoptosis induction through different pathways, such as caspase activation through the mitochondrial pathway [50,51], inhibition of the Akt signaling pathways [52,53], and cell cycle arrest in the G2/M phase [39,44,50,54]. These effects have been shown in vitro, but also in vivo [22].…”