Synergistic Antitumor Effect of Genitinib (Iressa®) with Flavonoids from the Scutellaria baicalensis Root on the Non-Small Cell Lung Cells
Y. Hirata1, *, M. Tatsu1, C. Amano1, Y. Kawaratani2, M. Hirata1, Y. Ohmomo1, Y. Nagaoka2, M. Shibano1, T. Sasaki3, S. Uesato2, M. Taniguchi1, *
1 Division of Pharmaceutical Science, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
2 Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan.
3 Department of Neurology, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
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.
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.
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.
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.
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