Investigation of U-251 cell death triggered by flavonoid luteolin: towards a better understanding on its anticancer property against glioblastomas

Abstract

Recently, many studies have reported the anticancer properties of flavonoid luteolin against a variety of tumors, but there is still a lack in the description of its mechanism of action. In attempt to better contribute to the literature, we evaluated the antiproliferative activity of luteolin extracted by Fridericia platyphylla in a panel of tumor cell lines representative of six different tissues. Luteolin presented antiproliferative activity for all the assessed tumor cell lines, being glioblastoma the most sensitive one. This compound was able to inhibit U-251 cells migration and tumorigenesis. Besides, luteolin leads U-251 tumor cells to apoptosis death by depolarisation of the mitochondrial membrane, ERK proteins phosphorylation, cleavage of PARP and Caspase 9, further inducing DNA damage by H2AX phosphorylation, which had not yet been described for glioblastomas. Altogether, our results reaffirm luteolin as a potential therapeutic drug.

Graphical Abstract

Keywords:

• Luteolin
• Brazilian plant species
• Fridericia platyphylla
• anticancer
• natural products
• glioblastoma

Acknowledgments

The authors thank Capes (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), Maranhão State Research Foundation - FAPEMA and FINEP for funding this research.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by Capes (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) (grants 2016/06137-6 – G.B.L. and 2016/02345-3 – Y.E.M.F.), Maranhão State Research Foundation - FAPEMA (grant 00863/16 - C.Q.R.) and FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT).