Abstract 3040: A novel methoxyflavanone from a Chinese medicinal herb (Perilla frutescens) induces G2/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma cells

• Published in: Cancer research (Chicago, Ill.) Vol. 76; no. 14_Supplement; p. 3040
• Main Authors: Mohamed, Amer Ali Abd El Hafeez, Fujimura, Takashi, Kamei, Rikiya, Hirakawa, Noriko, Baba, Kenji, Nakano, Miyako, Ono, Kazuhisa, Kawamoto, Seiji
• Format: Journal Article
• Language: English
• Published: 15.07.2016
• DOI: 10.1158/1538-7445.AM2016-3040
• ISSN: 0008-5472

Abstract Background: Perilla frutescens is a common traditional Chinese medicinal herb used for a variety of diseases, e.g. allergic asthma, cough and intestinal disorders. Flavonoids isolated from P. frutescens such as rosmarinic acid, caffeic acid and apigenin have been reported to inhibit proliferation of a variety of cancer cell lines. We recently identified a novel methoxyflavanone named PDMF (Perilla-derived methoxyflavanone) from P. frutescens as a candidate for anti-allergic drug. The objective of the study is to investigate antitumor potency of PDMF on A549 human lung adenocarcinoma and to elucidate its carcinostatic mechanisms. Methods: Effect of PDMF on cell proliferation and viability of A549 cells were assessed by BrdU incorporation assay and trypan blue dye exclusion test. Cell cycle and apoptosis analyses were carried out by flow cytometry. To elucidate antitumor mechanisms of PDMF, expression and activation status of cell cycle/apoptosis regulators (p53/p21/BAX/caspases) were thoroughly analyzed by immunoblotting. Results: Stimulation with PDMF not only triggered G2/M cell cycle arrest but also induced apoptosis of A549 cells in a dose-dependent manner. Mechanistically, PDMF stimulation significantly induced protein levels of p53 and its phosphorylated active forms (pSer15) accompanied by induction of p21 and BAX. We also found that proapoptotic caspase molecules (caspase 3, 8, and 9) were all activated upon stimulation with PDMF. Conclusion: These results suggest that this Perilla-derived methoxyflavanone represents a useful cancer-preventive phytochemical that triggers G2/M arrest, apoptosis, and activation of p53 pathway. Citation Format: Amer Ali Abd El Hafeez Mohamed, Takashi Fujimura, Rikiya Kamei, Noriko Hirakawa, Kenji Baba, Miyako Nakano, Kazuhisa Ono, Seiji Kawamoto. A novel methoxyflavanone from a Chinese medicinal herb (Perilla frutescens) induces G2/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3040.