A methoxyflavanone derivative from the Asian medicinal herb (Perilla frutescens) induces p53-mediated G2/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma

Abstract

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 G2/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 p21Cip1/Waf1 and proapoptotic caspases, caspase-9 and caspase-3. We also found that small interfering RNA knockdown of p53 completely abolished the PDMF-induced G2/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 G2/M cell cycle arrest and apoptosis.

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Acknowledgements

This work was financially supported by the Mishima Food Co., Ltd. N. Hirakawa and K. Baba are employees of the Mishima Food Co., Ltd. Abd El-Hafeez A. A. was supported by the Ministry of Education, Culture, Sports, Science, and Technology, MEXT, Japan.

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Correspondence to Seiji Kawamoto.

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Abd El-Hafeez, A.A., Fujimura, T., Kamei, R. et al. A methoxyflavanone derivative from the Asian medicinal herb (Perilla frutescens) induces p53-mediated G2/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma. Cytotechnology 70, 899–912 (2018). https://doi.org/10.1007/s10616-017-0116-1

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Keywords

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