A methoxyflavanone derivative from the Asian medicinal herb (Perilla frutescens) induces p53-mediated G(2)/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma

作者：Abd El Hafeez Amer Ali; Fujimura Takashi; Kamei Rikiya; Hirakawa Noriko; Baba Kenji; Ono Kazuhisa; Kawamoto Seiji^*

来源：Cytotechnology, 2018, 70(3): 899-912.

DOI：10.1007/s10616-017-0116-1

• Apoptosis
• Flavanone
• G2/M cell cycle arrest
• Lung cancer
• p53
• Perilla frutescens

Perilla frutescens is an Asian dietary herb consumed as an essential seasoning in Japanese cuisine as well as used for a Chinese medicine. Here, we report that a newly found methoxyflavanone derivative from P. frutescens (Perilla-derived methoxyflavanone, PDMF; 8-hydroxy-5,7-dimethoxyflavanone) shows carcinostatic activity on human lung adenocarcinoma, A549. We found that treatment with PDMF significantly inhibited cell proliferation and decreased viability through induction of G(2)/M cell cycle arrest and apoptosis. The PDMF stimulation induces phosphorylation of tumor suppressor p53 on Ser15, and increases its protein amount in conjunction with up-regulation of downstream cyclin-dependent kinase inhibitor p21(Cip1/Waf1) and proapoptotic caspases, caspase-9 and caspase-3. We also found that small interfering RNA knockdown of p53 completely abolished the PDMF-induced G(2)/M cell cycle arrest, and substantially abrogated its proapoptotic potency. These results suggest that PDMF represents a useful tumor-preventive phytochemical that triggers p53-driven G(2)/M cell cycle arrest and apoptosis.

• 出版日期2018-6