PLoS ONE (Jan 2018)

Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition.

  • Gabriel Silva,
  • Mozart Marins,
  • Nadda Chaichanasak,
  • Yongdae Yoon,
  • Ana Lúcia Fachin,
  • Vitor Caressato Pinhanelli,
  • Luis Octávio Regasini,
  • Mariana Bastos Dos Santos,
  • Gabriela Miranda Ayusso,
  • Beatriz de Carvalho Marques,
  • Wells W Wu,
  • Je-Nie Phue,
  • Rong-Fong Shen,
  • Seung Joon Baek

DOI
https://doi.org/10.1371/journal.pone.0202263
Journal volume & issue
Vol. 13, no. 8
p. e0202263

Abstract

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Naturally-occurring chalcones and synthetic chalcone analogues have been demonstrated to have many biological effects, including anti-inflammatory, anti-malarial, anti-fungal, and anti-oxidant/anti-cancerous activities. Compared to other chalcones, trans-chalcone exhibits superior inhibitory activity in cancer cell growth as shown via in vitro assays, and exerts anti-cancerous effects via the activation of the p53 tumor suppressor protein. Thus, characterization of the specific mechanisms, by which trans-chalcone activates p53, can aid development of new chemotherapeutic drugs that can be used individually or synergistically with other drugs. In this report, we found that trans-chalcone modulates many p53 target genes, HSP40 being the most induced gene in the RNA-Seq data using trans-chalcone-treated cells. CRM1 is also inhibited by trans-chalcone, resulting in the accumulation of p53 and other tumor suppressor proteins in the nucleus. Similar effects were seen using trans-chalcone derivatives. Overall, trans-chalcone could provide a strong foundation for the development of chalcone-based anti-cancer drugs.