Involvement of the antioxidative property of morusin in blocking phorbol ester–induced malignant transformation of JB6 P+ mouse epidermal cells

Pai Shan Cheng, Chao Chin Hu, Chau Jong Wang, Yean Jang Lee, Wei Chia Chung, Tsui Hwa Tseng*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

Chemoprevention has been acknowledged as an important and practical strategy for managing cancer. We have previously synthesized morusin, a prenylated flavonoid that exhibits anti–cancer progression activity. In the present study, we evaluated the anti–cancer promotion potential of morusin by using the mouse epidermal JB6 P+ cell model. Extensive evidence shows that tumor promotion by phorbol esters is due to the stimulation of reactive oxygen species (ROS). Therefore, the effect of morusin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ROS production was assessed. Noncytotoxic concentrations of morusin were found to dose-dependently reduce TPA-induced ROS production. Moreover, morusin inhibited TPA-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activation, which can mediate cell proliferation and malignant transformation. Furthermore, morusin inhibited the TPA upregulation of cyclooxygenase 2 (COX-2), which may be regulated by AP-1 and NF-κB. In addition, noncytotoxic concentrations of morusin reduced the TPA-promoted cell growth of JB6 P+ cells and inhibited TPA-induced malignant properties, such as cytoskeletal rearrangement and cell migration of JB6 P+ cells. Similar to the effects of glutathione (GSH) pretreatment, morusin inhibited TPA-induced expression of N-cadeherin and vimentin, which are malignant cell surface proteins. Finally, morusin treatment dose-dependently suppressed the TPA-induced anchorage-independent cell transformation of JB6 P+ cells. In conclusion, our results evidence that morusin possesses anti–cancer promotion potential because of its antioxidant property, which mediates multiple transformation–associated gene expression.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalChemico-Biological Interactions
Volume264
DOIs
StatePublished - 25 02 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

  • JB6 P cells
  • Morusin
  • TPA
  • Transformation

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