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

Oncol Lett. 2019 Apr;17(4):3842-3850. doi: 10.3892/ol.2019.10052. Epub 2019 Feb 19.


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.

Keywords: breast cancer; cell cycle; hTERT; luteolin; telomerase.