English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The transcription factor hypoxia-inducible factor-1 (HIF-1) consists of oxygen-sensitive HIF-1α and constitutive HIF-1β. HIF-1α is undetectable in normal cells, but cancer cells frequently express HIF-1α to support their growth, angiogenesis, and high glycolysis (also known as the Warburg effect). The Warburg effect in cancer cells increases energy expenditure and thus participates in cancer-induced metabolic disorder, cancer cachexia. In the present study, we investigated whether two components of Rheum palmatum, emodin and rhein, inhibited HIF-1α expression in human pancreatic cancer cells and whether the inhibiting effect, if any, attenuated cancer cachexia. Using Western blotting, we demonstrated that emodin and rhein decreased HIF-1α expression in MiaPaCa2 and four other human pancreatic cancer cell lines. We also examined HIF-1α expression when MiaPaCa2 cells were exposed to PX-478, noscapine, and phenethyl isothiocyanate, as these compounds were known to inhibit HIF-1α expression in different cancer cells. PX-478 and noscapine inhibited HIF-1α expression to a less extent than emodin and rhein, and phenethyl isothiocyanate did not inhibit HIF-1α expression in tested concentrations. We obtained evidence that emodin and rhein decreased HIF-1α by decreasing its biosynthesis but not gene transcription or protein stability. When MiaPaCa2 cells were implanted in athymic mice, emodin and rhein inhibited cancer-cell growth and HIF-1α expression. In these athymic mice, emodin and rhein also attenuated two pathological constituents of cancer cachexia, namely high hepatic gluconeogenesis and skeletal-muscle proteolysis. In conclusion, emodin and rhein decrease pancreatic cancer cell's growth and HIF-1α expression and attenuate cancer cachexia in the athymic mice carrying the cancer cells.

oncotarget

Emodin and rhein decrease levels of hypoxia-inducible factor-1α in human pancreatic cancer cells and attenuate cancer cachexia in athymic mice carrying these cells