Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1-DNA-complex formation

Midori A. Arai, Kyoko Uchida, Samir K. Sadhu, Firoj Ahmed, Masami Ishibashi

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Hedgehog (Hh) signaling plays an important role in embryonic development, cell maintenance and cell proliferation. Moreover, Hh signaling contributes to the growth of cancer cells. Physalins are highly oxidized natural products with a complex structure. Physalins (1-7) were isolated from Solanum nigrum (Solanaceae) collected in Bangladesh by using our cell-based assay. The isolated physalins included the previously reported Hh inhibitors 5 and 6. Compounds 1 and 4 wed strong inhibition of GLI1 transcriptional activity, and exhibited cytotoxicity against cancer cell lines with an aberrant activation of Hh signaling. Compound 1 inhibited the production of the Hh-related proteins patched (PTCH) and BCL2. Analysis of the structures of different physalins showed that the left part of the physalins was important for Hh inhibitory activity. Interestingly, physalin H (1) disrupted GLI1 binding to its DNA binding domain, while the weak inhibitor physalin G (2) did not show inhibition of GLI1-DNA complex formation.

Original languageEnglish
Pages (from-to)134-140
Number of pages7
JournalBeilstein Journal of Organic Chemistry
Volume10
DOIs
Publication statusPublished - 2014 Jan 13
Externally publishedYes

Keywords

  • Hedgehog inhibitor
  • Hedgehog signal
  • Natural products
  • Physalins
  • Solanum nigrum

ASJC Scopus subject areas

  • Organic Chemistry

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