Ingenol mebutate inhibits the growth of pancreatic cancer cells in vitro via STING with an efficacy comparable to that of clinically used anticancer agents

Fumihiro Kikuyama, Sayo Suzuki, Aya Jibiki, Yuta Yokoyama, Hitoshi Kawazoe, Susumu Kitanaka, Tomonori Nakamura

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Pancreatic cancer is associated with a poor prognosis; thus, there is an urgent need to develop new and effective treatments. Ingenol mebutate (IM), which is isolated from the latex of Euphorbia peplus, was recently shown to be effective against pancreatic cancer cell lines; however, its mechanism of action has not been fully elucidated. In this study, we focused on the less drug-sensitive pancreatic cancer cell line Panc-1 and compared IM to commercially available anticancer drugs using cell survival assays. In addition, we aimed to identify novel biomolecules that may be involved in the mechanism of action of IM using RNA sequencing, western blotting, and inhibition assays. The IC50 values after 72 h of exposure to IM and SN-38, drugs to which the Panc-1 cells are most sensitive among the tested anticancer agents, were 43.1 ± 16.8 nM and 165 ± 37 nM, respectively. IM showed a cytostatic effect equal to or greater than that of the clinically used pancreatic cancer therapeutic drugs. RNA sequencing and protein expression analysis revealed that expression of stimulator of interferon genes (STING) increased at low IM concentration, whereas cell viability decreased. Co-exposure of IM and STING inhibitor, H-151, to Panc-1 or MIA PaCa-2 cell lines canceled the growth-inhibitory effects of IM alone. In conclusion, IM may have an efficacy comparable to that of existing pancreatic cancer therapeutic agents on the less drug-sensitive Panc-1 cell line and the immune-related molecule STING plays a role in the mechanism of action of IM.

Original languageEnglish
Pages (from-to)343-351
Number of pages9
JournalJournal of Natural Medicines
Volume77
Issue number2
DOIs
Publication statusPublished - 2023 Mar

Keywords

  • Anticancer agents
  • Euphorbia peplus
  • Ingenol mebutate
  • Pancreatic cancer
  • STING

ASJC Scopus subject areas

  • Molecular Medicine

Fingerprint

Dive into the research topics of 'Ingenol mebutate inhibits the growth of pancreatic cancer cells in vitro via STING with an efficacy comparable to that of clinically used anticancer agents'. Together they form a unique fingerprint.

Cite this