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Cytotechnology. 2018 Jun;70(3):913-919. doi: 10.1007/s10616-017-0124-1. Epub 2017 Jul 29.

Synergistic tumor suppression by a Perilla frutescens-derived methoxyflavanone and anti-cancer tyrosine kinase inhibitors in A549 human lung adenocarcinoma.

Author information

1
Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, 739-8530, Japan.
2
Mishima Food Co. Ltd., Hiroshima, Japan.
3
Department of Food Sciences and Biotechnology, Faculty of Life Sciences, Hiroshima Institute of Technology, Hiroshima, Japan.
4
Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, 739-8530, Japan. skawa@hiroshima-u.ac.jp.

Abstract

Anti-cancer tyrosine kinase inhibitors (TKIs) are effective in many types of cancers including non-small cell lung cancer, while appearance of TKI-resistant tumors suggests a need for the development of their potentiation strategies. We have previously shown that a methoxyflavanone derivative from the Asian medicinal herb Perilla frutescens (Perilla-derived methoxyflavanone; PDMF) shows a prominent anti-tumor activity against A549 human lung adenocarcinoma. Here we show that PDMF and anti-cancer TKIs (nilotinib, bosutinib, dasatinib, and ponatinib) synergistically suppress proliferation of A549 cells. Flow cytometric analysis indicated that co-stimulation with nilotinib (4 μM) and PDMF induced G2/M cell cycle arrest in low PDMF doses (10-50 μM), whereas this combination triggered de novo G1 arrest in higher PDMF dosages (50-125 μM). We also found that co-administration with nilotinib and PDMF significantly suppressed in vivo tumorigenicity of A549 cells in athymic nude mice.

KEYWORDS:

A549 cells; Lung cancer; Methoxyflavanone; Perilla frutescens; Tyrosine kinase inhibitors

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