The Open Plant Science Journal
2017, 10 : 62-69Published online 2017 July 31. DOI: 10.2174/1874294701710010062
Publisher ID: TOPSJ-10-62
RESEARCH ARTICLE
Synergistic Antitumor Effect of Genitinib (Iressa) with Flavonoids from the Root on the Non-Small Cell Lung Cells
* Address correspondence to this author at Division of Pharmaceutical Science, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Tel: +81726901000; Fax: +817269010058; E-mails: y.hirata@gly.oups.ac.jp and taniguti@gly.oups.ac.jp
ABSTRACT
Background:
As was reported, gefitinib (Iressa®) showed a strong growth inhibitory effect on non-small-cell lung cancer PC-9 cells with mutant EGFR, but did not so much on A549 cells with wild-type EGFR.
Observation:
We here demonstrated by isobolograms and combination index analyses that the paired combinations of gefitinib with flavonoids from Wogon (Scutellaria baicalensis root): wogonin, oroxylin A and chrysin exerted synergistic anti-tumor effects against A549 cells.
Result:
The cell cycle analyses revealed that the combination of gefitinib and oroxylin A in A549 cells induced more apoptotic cells than other paired combinations as well as gefitinib alone. Thus, it is anticipated that oroxylin A could help to enhance the remission rate in the gefitinib therapy for the patients with non-small cell cancer cells with wild-type EGFR which provide a poor prognosis.
Conclusion:
Since the Wogon flavonoids, wogonin, oroxylin A and chrysin, accelerated the acetylation of Lysine residues of histone proteins, it is suggested that they put forth anti-tumor activities through inhibition of histone deacetylases which mediated the post-translational modification of histones.