Induction of human leukemia cell differentiation via PKC/MAPK pathways by arsantin, a sesquiterpene lactone from Artemisia santolina

Sin Ho Kweon, Ju Han Song, Hee Jin Kim, Tae Sung Kim, Bo Gil Choi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Sesquiterpene lactone compounds have received considerable attention in pharmacological research due to their therapeutic effects including anti-cancer and anti-inflammatory activities. In this report, we investigated the effect of arsantin, a sesquiterpene lactone compound present in Artemisia santolina, on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Arsantin significantly induced HL-60 cell differentiation in a concentration-dependent manner. Cytofluorometric analysis indicated that arsantin induced HL-60 cell differentiation predominantly into granulocytes. Both PKC and MAPK inhibitors suppressed the HL-60 cell differentiation induced by arsantin. Moreover, treatment with arsantin increased protein levels of PKCα and PKCβII isoforms, and also induced increased protein levels and phosphorylation form of MAPKs in HL-60 cells. Importantly, arsantin synergistically enhanced differentiation of HL-60 cells in a dose-dependent manner when combined with either low doses of 1,25-(OH)2D3 or ATRA. The ability to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA by arsantin may improve outcomes in the therapy of acute promyelocytic leukemia.

Original languageEnglish
Pages (from-to)2020-2028
Number of pages9
JournalArchives of Pharmacal Research
Volume38
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

Keywords

  • Arsantin
  • HL60 differentiation
  • MAPK
  • Protein kinase C
  • Sesquiterpene lactone

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Organic Chemistry

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