ArticleEukaryotic cell2011
Sampangine inhibits heme biosynthesis in both yeast and human.
Article in Eukaryotic cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Heme Causes Pain in Sickle MiceAntioxidants & redox signaling · 2021Article
- Oxoisoaporphines and Aporphines: Versatile Molecules with Anticancer Effects.Molecules (Basel, Switzerland) · 2019Review
- Novel Cell-Killing Mechanisms of Hydroxyurea and the Implication toward Combination Therapy for the Treatment of Fungal Infections.Antimicrobial agents and chemotherapy · 2017Article
- Increased heme synthesis in yeast induces a metabolic switch from fermentation to respiration even under conditions of glucose repression.The Journal of biological chemistry · 2017Article
- Heme deficiency sensitizes yeast cells to oxidative stress induced by hydroxyurea.The Journal of biological chemistry · 2017Article
- New Horizons in Antifungal Therapy.Journal of fungi (Basel, Switzerland) · 2016Review
- An extended set of yeast-based functional assays accurately identifies human disease mutations.Genome research · 2016Article
- Identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis.The Journal of antimicrobial chemotherapy · 2016Article
- Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids.mBio · 2015Article
- Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy.PLoS genetics · 2012Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The azaoxoaporphine alkaloid sampangine exhibits strong antiproliferation activity in various organisms. Previous studies suggested that it somehow affects heme metabolism and stimulates production of reactive oxygen species (ROS). In this study, we show that inhibition of heme biosynthesis is the primary mechanism of action by sampangine and that increases in the levels of reactive oxygen species are secondary to heme deficiency. We directly demonstrate that sampangine inhibits heme synthesis in the yeast Saccharomyces cerevisiae. It also causes accumulation of uroporphyrinogen and its decarboxylated derivatives, intermediate products of the heme biosynthesis pathway. Our results also suggest that sampangine likely works through an unusual mechanism-by hyperactivating uroporhyrinogen III synthase-to inhibit heme biosynthesis. We also show that the inhibitory effect of sampangine on heme synthesis is conserved in human cells. This study also reveals a surprising essential role for the interaction between the mitochondrial ATP synthase and the electron transport chain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.