Effects of eflornithine: A Synthesis of Findings from 27 Studies

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Original Abstract of the Article

Major Research Findings

Eflornithine (DFMO) is a drug that inhibits polyamine synthesis by inhibiting the enzyme ornithine decarboxylase (ODC). ODC is the rate-limiting enzyme in polyamine biosynthesis, which plays a crucial role in cell growth and differentiation. Various studies have shown that DFMO can suppress the growth of various cancer cells. 26 , 4 , 18 , 12 , 14 , 5 , 10 Additionally, DFMO has been reported to inhibit the replication of hepatitis B virus (HBV). 20 DFMO is thought to inhibit HBV replication by reducing the stability of the HBV core protein (HBc). 20 Furthermore, DFMO has been suggested to regulate glucose homeostasis by inhibiting the activation of ODC, which plays a role in promoting the release of the glucose transporter SGLT1 from the cell. 24 Due to these significant roles in various cellular processes such as cell growth, viral replication, and glucose homeostasis, DFMO has potential for therapeutic applications in cancer, infectious diseases, and metabolic disorders.

Benefits and Risks

Benefits Summary

DFMO has been shown to suppress the growth of various cancer cells. For example, it has been reported to suppress the growth of ovarian cancer cells, neuroblastoma cells, and esophageal squamous cell carcinoma cells. 26 , 14 , 12 , 10 DFMO has also been reported to inhibit the replication of hepatitis B virus (HBV). 20 Furthermore, DFMO has been suggested to regulate glucose homeostasis by inhibiting the activation of ODC, which plays a role in promoting the release of the glucose transporter SGLT1 from the cell. 24

Risk Summary

DFMO is generally considered a safe drug, but side effects such as nausea, vomiting, diarrhea, loss of appetite, anemia, and liver dysfunction have been reported. Administration to pregnant or breastfeeding women should be carefully considered due to potential effects on the fetus or infant.

Comparison of Studies

Commonalities

Many studies have shown that DFMO inhibits cell growth by inhibiting polyamine synthesis. 26 , 4 , 18 , 12 , 14 , 5 , 10 Additionally, DFMO has been reported to be effective against various cancer cells and hepatitis B virus. 20 , 26 , 14 , 12 , 10

Differences

The effects of DFMO have been reported to vary depending on the cell type and disease condition. 26 , 14 , 12 , 10 For example, DFMO has been shown to be more effective against neuroblastoma cells when combined with other drugs than when administered alone. 14 Additionally, DFMO has been shown to induce apoptosis in ovarian cancer cells, but it has been shown to suppress neuroblastoma cell growth by stopping the cell cycle rather than inducing apoptosis. 26 , 14 Furthermore, DFMO has been shown to inhibit the replication of hepatitis B virus by reducing the stability of the HBc protein, but such effects have not been reported for other viruses. 20

Consistency and Contradictions

Many studies have shown that DFMO inhibits cell growth, but the effects of DFMO have been reported to vary depending on the cell type and disease condition. Therefore, further research is needed to apply DFMO to various diseases.

Notes on Real-Life Application

DFMO has the potential to be used to treat various diseases, but it is important to be cautious about its application in real life due to side effects and individual differences in its effects. It is essential to consult a doctor before taking DFMO and to ensure that it is appropriate for your body.

Limitations of Current Research

Current research has shown that the effects of DFMO vary depending on the cell type and disease condition, but the mechanisms underlying these differences are not yet fully understood. Long-term safety of DFMO also requires further investigation.

Future Research Directions

Future research should focus on elucidating the mechanisms of DFMO action and developing more effective treatments. Long-term safety of DFMO also needs further research.

Conclusion

DFMO is a drug with potential therapeutic applications in various diseases. However, the effects of DFMO have been reported to vary depending on the cell type and disease condition. Therefore, further research is needed to apply DFMO to various diseases. It is essential to consult a doctor before taking DFMO and to ensure that it is appropriate for your body.

Literature analysis of 27 papers
Positive Content
23
Neutral Content
1
Negative Content
3
Article Type
0
0
1
3
27
2.

A pilot study of genomic-guided induction therapy followed by immunotherapy with difluoromethylornithine maintenance for high-risk neuroblastoma.

Author: KravekaJacqueline M, LewisElizabeth C, BergendahlGenevieve, FergusonWilliam, OesterheldJavier, KimElizabeth, NagulapallyAbhinav B, DykemaKarl J, BrownValerie I, RobertsWilliam D, MitchellDeanna, EslinDon, HansonDerek, IsakoffMichael S, WadaRandal K, HarrodVirginia L, RawwasJawhar, HannaGina, HendricksWilliam P D, ByronSara A, SnuderlMatija, SerranoJonathan, TrentJeffrey M, Saulnier ShollerGiselle L

Improved survival

This study evaluated the safety and feasibility of adding targeted agents to induction therapy and adding DFMO to immunotherapy for high-risk neuroblastoma (HRNB). The addition of targeted agents did not lead to toxicities that required dose reduction of chemotherapy or permanent discontinuation of the targeted agent. DFMO was well-tolerated and resulted in no unexpected adverse events.

Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation.

Author: HyvönenMervi T, UcalSebahat, PasanenMarkku, PeräniemiSirpa, WeisellJanne, KhomutovMaxim, KhomutovAlex R, VepsäläinenJouko, AlhonenLeena, KeinänenTuomo A

Decreased ROS levels
Inhibited ODC activity
Inhibited TCA cycle
Inhibited amine oxidases
Inhibited eIF5A formation
Inhibited polyamine uptake

This study found that triethylenetetramine (TETA) inhibited polyamine metabolism in prostate, breast, and choriocarcinoma cells. TETA induced antizyme, down-regulated ornithine decarboxylase, and inhibited polyamine uptake.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

The involvement of polyamine uptake and synthesis pathways in the proliferation of neonatal astrocytes.

Author: Malpica-NievesChristian J, Rivera-AponteDavid E, Tejeda-BayronFlavia A, MayorAngel M, PhanstielOtto, VehRüdiger W, EatonMisty J, SkatchkovSerguei N

Astrocyte proliferation

This study investigated the contribution of uptake and/or synthesis of polyamines (PAs) to proliferation in neonatal astrocytes. The results suggest that neonatal astrocytes synthesize sufficient quantities of PAs de novo but are also able to import exogenous PAs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.

Author: ImamuraMasataka, HigashiKyohei, YamaguchiKatsutoshi, AsakuraKiryu, FurihataTomomi, TeruiYusuke, SatakeToshihiko, MaegawaJiro, YasumuraKazunori, IbukiAi, AkaseTomoko, NishimuraKazuhiro, KashiwagiKeiko, LinhardtRobert J, IgarashiKazuei, ToidaToshihiko

Polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. This study found that the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Let-7b, a member of the let-7 microRNA family, suppresses initiation codon recognition by 43S preinitiation complex during EXT2 translation. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Refractive Index Sensing for Measuring Single Cell Growth.

Author: CetinArif E, TopkayaSeda Nur, Yalcin-OzuysalOzden, KhademhosseiniAli

Cell growth measurement

A plasmonic platform can measure cell weight and growth dynamics in real-time for adherent cells. This technology can assess cell growth profiles and heterogeneity, determine the effects of intracellular metabolism, and evaluate drug responses.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

DFMO Carbon Dots for Treatment of Neuroblastoma and Bioimaging.

Author: PaudyalSuraj, VallejoFrederic Anthony, CilingirEmel Kirbas, ZhouYiqun, MintzKeenan J, PressmanYelena, GuJun, VanniSteven, GrahamRegina M, LeblancRoger M

Neuroblastoma treatment

This study synthesized carbon dots (CDs) using difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor used in neuroblastoma treatment. These DFMO CDs effectively reduced cell viability in neuroblastoma cell lines at significantly lower concentrations than conventional DFMO, demonstrating a robust advantage. Bioimaging and DNA electrophoresis revealed that DFMO CDs can enter the nucleus of cells and interact with DNA. The study suggests that DFMO CDs have potential as a novel therapeutic agent for neuroblastoma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Hypoxic Proliferation of Osteosarcoma Cells Depends on Arginase II.

Author: SettyBhuvana A, JinYi, HoughtonPeter J, YeagerNicholas D, GrossThomas G, NelinLeif D

Increased cell proliferation

Hypoxic conditions have been demonstrated in solid tumors and are associated with increased cell proliferation and angiogenesis. This study hypothesized that hypoxia would increase cellular proliferation via arginase induction in human osteosarcoma cell lines.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial.

Author: Betu KumesoVictor Kande, KalonjiWilfried Mutombo, RembrySandra, Valverde MordtOlaf, Ngolo TeteDigas, PrêtreAdeline, DelhommeSophie, Ilunga Wa KyhiMédard, CamaraMamadou, CatusseJulie, SchneitterStefan, NusbaumerMorgane, Mwamba MiakaErick, Mahenzi MbemboHélène, Makaya MayawulaJoseph, Layba CamaraMariame, Akwaso MassaFélix, Kaninda BadibabiLewis, Kasongo BonamaAugustin, Kavunga LukulaPapy, Mutanda KalonjiSylvain, Mariero PhilemonPhyll, Mokilifi NganyonyiRicardo, Embana MankiaraHugues, Asuka Akongo NgubaAndré, Kobo MuanzaVincent, Mulenge NasandhelErnest, Fifi Nzeza BambuwuAimée, ScherrerBruno, Strub-WourgaftNathalie, TarralAntoine

HAT treatment
Unknown

This study aims to assess the safety and efficacy of acoziborole in adult and adolescent patients with gambiense HAT, a late-stage form of human African trypanosomiasis.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Effects of oral administration of synthesized delta-amides of eflornithine in the rat.

Author: HelenaKevin J, N'DaDavid D, JohanssonCarl C, BreytenbachJaco C, AshtonMichael

Poor intestinal absorption

This study synthesized delta-amide derivatives of eflornithine and evaluated their physicochemical properties and intestinal absorption in rats. The derivatives were found to be more lipophilic than eflornithine, but they were not absorbed from the gastrointestinal tract or metabolized into eflornithine in vivo. This suggests that these derivatives are not suitable for oral administration of eflornithine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Investigational drugs currently in phase II clinical trials for actinic keratosis.

Author: LozziFlavia, LannaCaterina, MazzeoMauro, GarofaloVirginia, PalumboVincenzo, MazzilliSara, DiluvioLaura, TerrinoniAlessandro, BianchiLuca, CampioneElena

Field-directed therapies
Lesion relapse
Squamous cell carcinoma

Actinic keratoses (AKs), caused by sun damage, require field-directed therapies to prevent recurrence and potential progression to squamous cell carcinoma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis: A critical appraisal of 23 years of experience in the Democratic Republic of Congo.

Author: KazumbaLéon Mbiyangandu, KakaJean-Claude Tshinzobe, NgoyiDieudonné Mumba, Tshala-KatumbayDésiré

Cytorachy
Protidorachy
Sleeping sickness mortality

Clinical dysfunction on admission, high protidorachy, the presence of parasites in the CSF, and high cytorachy were significant predictors of death in patients with advanced stage-2 sleeping sickness.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

20.

Difluoromethylornithine, a Decarboxylase 1 Inhibitor, Suppresses Hepatitis B Virus Replication by Reducing HBc Protein Levels.

Author: MaoBinli, WangZhuo, PiSidie, LongQuanxin, ChenKe, CuiJing, HuangAilong, HuYuan

HBV treatment

Difluoromethylornithine (DFMO), an inhibitor of decarboxylase 1(ODC1), was found to inhibit HBV replication by reducing the stability of the HBc protein. This discovery suggests a novel approach for HBV therapeutics.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons.

Author: OesterheldJavier, FergusonWilliam, KravekaJacqueline M, BergendahlGenevieve, ClinchThomas, LorenziElizabeth, BerryDon, WadaRandal K, IsakoffMichael S, EslinDon E, BrownValerie I, RobertsWilliam, ZagePeter, HarrodVirginia L, MitchellDeanna S, HansonDerek, Saulnier ShollerGiselle L

Improved EFS
Improved OS

This study re-analyzes data from a previous trial to further evaluate the effectiveness of eflornithine (DFMO) as a maintenance therapy for high-risk neuroblastoma (HRNB) after immunotherapy. The analysis suggests that DFMO may improve event-free survival (EFS) and overall survival (OS) compared to historical rates.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

The Long Wait for a New Drug for Human African Trypanosomiasis.

Author: BakerCatriona H, WelburnSusan C

HAT treatment
Toxicity

Current treatments for human African trypanosomiasis (HAT) are limited and often problematic. This study explores the challenges of drug development for this neglected disease and examines the epidemiological, political, social, and economic factors influencing research efforts.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

23.

DFMO and 5-Azacytidine Increase M1 Macrophages in the Tumor Microenvironment of Murine Ovarian Cancer.

Author: TraversMeghan, BrownStephen M, DunworthMatthew, HolbertCassandra E, WiehagenKarla R, BachmanKurtis E, FoleyJackson R, StoneMeredith L, BaylinStephen B, CaseroRobert A, ZahnowCynthia A

Increased survival
Ovarian cancer treatment
Reduced tumor burden

A combination therapy of 5-Azacytidine (5AZA-C) and α-difluoromethylornithine (DFMO) significantly increased survival and decreased tumor burden in an immunocompetent mouse model for ovarian cancer. This therapy led to a striking increase in activated T cells and NK cells and a decrease in immunosuppressive macrophages, suggesting that it modifies macrophage polarization in the tumor microenvironment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

25.

Recognition of Potential COVID-19 Drug Treatments through the Study of Existing Protein-Drug and Protein-Protein Structures: An Analysis of Kinetically Active Residues.

Author: PerišićOgnjen

COVID-19 treatment

This study is based on the analysis of normal modes of proteins and indicates that small molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

27.

Chemotherapy for second-stage human African trypanosomiasis: drugs in use.

Author: LutjeVittoria, ProbynKatrin, SeixasJorge, BergmanHanna, VillanuevaGemma

Improved treatment outcomes
None mentioned

This review examines the effectiveness and safety of drugs used to treat the second stage of Trypanosoma brucei gambiense trypanosomiasis, a fatal disease if left untreated.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

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