Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis

Henrik Fyrst, Babak Oskouian, Padmavathi Bandhuvula, Yaqiong Gong, Hoe Sup Byun, Robert Bittman, Andrew R. Lee, Julie D. Saba

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Sphingolipid metabolites regulate cell proliferation, migration, and stress responses. Alterations in sphingolipid metabolism have been proposed to contribute to carcinogenesis, cancer progression, and drug resistance. We identified a family of natural sphingolipids called sphingadienes and investigated their effects in colon cancer. We find that sphingadienes induce colon cancer cell death in vitro and prevent intestinal tumorigenesis in vivo. Sphingadienes exert their influence by blocking Akt translocation from the cytosol to the membrane, thereby inhibiting protein translation and promoting apoptosis and autophagy. Sphingadienes are orally available, are slowly metabolized through the sphingolipid degradative pathway, and show limited short-term toxicity. Thus, sphingadienes represent a new class of therapeutic and/or chemopreventive agents that blocks Akt signaling in neoplastic and preneoplastic cells.

Original languageEnglish
Pages (from-to)9457-9464
Number of pages8
JournalCancer research
Volume69
Issue number24
DOIs
StatePublished - Dec 15 2009

Fingerprint

Dive into the research topics of 'Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis'. Together they form a unique fingerprint.

Cite this