Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase

Abstract

Luteolin is a flavonoid, which has been extensively investigated due to its antitumor effects; however, the underlying mechanisms of its action remain largely unknown. The present study aimed to investigate the role of luteolin in breast cancer (BC), and explored how luteolin suppresses the growth and induces the apoptosis of BC cells. The MTS assay was used to determine the anticancer activity of luteolin. Colony formation and Transwell assays were performed to evaluate the effects of luteolin on cell growth and invasion. Cell cycle progression and apoptosis were analyzed by flow cytometry. In addition, western blotting was performed to analyze cellular apoptosis and signaling pathways elicited by luteolin. The present study revealed that the proliferation of the BC cell line MDA-MB-231 was effectively suppressed by luteolin in a dose-dependent manner. Additionally, luteolin was revealed to increase apoptotic rates in BC cells. Dose-dependent cell cycle arrest in S phase was observed following treatment with luteolin in MDA-MB-231 cells. Mechanistically, luteolin reduced telomerase levels in a dose-dependent manner. Additionally, luteolin inhibited phosphorylation of the nuclear factor-κB inhibitor α and its target gene c-Myc, to suppress human telomerase reverse transcriptase (hTERT) expression, which encodes the catalytic subunit of telomerase. Collectively, the results of the present study indicated that luteolin may inhibit BC cell growth by targeting hTERT, suggesting that the mechanism of hTERT regulation by luteolin may justify further study regarding its potential as a therapeutic target for BC treatment.

Luteolin exhibits anti-breast cancer property through up-regulating miR-203

“…Excessive proliferation is one main character of human cancers. The anti-proliferating and pro-death functions of luteolin in breast cancer cells have been previously revealed [23,30]. This was also observed in this study that MCF-7 and MDA-MB-453 cells viability was repressed while apoptosis was induced by luteolin.…”

“…Powder luteolin (!98% (TLC)) from Sigma-Aldrich (St. Louis, MO) was dissolved in DMSO to form a storage solution with 0.5 M. The storage solution was thinned by culture medium to make working solution with 10 lM. Cells were administrated by 10 lM luteolin for 24 as elsewhere described [23].…”

Luteolin Suppresses the Proliferation of Gastric Cancer Cells and Acts in Synergy with Oxaliplatin

“…Natural plant extracts and their flavonoids have exhibited anticancer properties both in vivo and in vitro. LUT, a flavonoid that is widely found in many natural plants such as honeysuckle, exhibits many biological effects such as free radical scavenging [25], as well as anti-inflammatory [14] and antitumor properties [16]. The antitumor activity of LUT has been investigated in diverse cancer models [26].…”

“…Luteolin (LUT, Figure 1(b)) is a flavonoid which is abundantly found in vegetables and fruits such as celery, broccoli, carrots, and peppers [13]. LUT has various biological functions such as being anti-inflammatory [14], antiatherogenic [15], and having antitumor effects [16]. In addition, LUT was shown to reduce proliferation and induce apoptosis in human osteosarcoma cells by regulating the apoptotic proteins BCL-2, BAX, caspase-3, and survivin [17].…”

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

“…Another target of luteolin is the catalytic subunit of telomerase, hTERT, that is downregulated such as its transcriptional inducer, c-myc, by a mechanism in which the cytoplasmic inactive form of NF-kB is stabilized. As result, the progressive shortening of telomeres induces apoptosis [121]. Luteolin can also regulate IL-6 production, by binding competition to IL-6Rα receptor, that causes the reduction of signal transducer and activator of transcription 3 (STAT3) phosphorylation, responsible for the transcription of different genes involved in cancer initiation and progression [122].…”